RESUMO

Background: Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is a crucial factor in predicting responses to immunotherapy. This systematic review and meta-analysis focuses on the prevalence of PD-L1 expression and clinicopathological features among Hispanic/Latino (H/L) populations. Methods: Embase, LILACS, Medline, and Virtual Health Library were searched for studies that evaluated the prevalence of PD-L1 in H/L patients. The protocol was submitted to PROSPERO with ID CRD42023488547. We employed the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses to assess the methodological quality and applicability of the included studies. Meta-analyses were done to determine the prevalence using a random effects model. Results: The meta-analysis, encompassing 21 articles with 16,486, revealed that 80.2% of patients had PD-L1 expression data available (n=13,222). The prevalence calculated of PD-L1 expression in Latino NSCLC patients was 55% [95% confidence interval (CI): 0.54-0.55], with 31% (95% CI: 0.27-0.36) showing a tumoral proportion score (TPS) of 1-49%, and 23% (95% CI: 0.16-0.30) registering a TPS ≥50%. Higher expression was observed in male gender, smoking, adenocarcinoma subtypes, poor tumor differentiation, and advanced stages. PD-L1 expression was most frequent in EGFR wild-type status (82.5%) with a odds ratio (OR) 1.54 (95% CI: 1.24-1.92) and PD-L1 expression was associated with ALK positive (OR =1.54; 95% CI: 1.24-1.92). Conclusions: This meta-analysis provides a comprehensive overview of PD-L1 expression in NSCLC in the H/L population. The findings underscore the significant prevalence of PD-L1 expression and emphasize the relevance of immunotherapy in this population. Understanding the clinicopathological features associated with PD-L1 expression can contribute to tailored treatment strategies for NSCLC in Latin America.

RESUMO

The modes of formation and release of secretion are complex processes that occur in secretory ducts and their description has great divergence in some species. The use of modern techniques to detect hydrolytic enzymes, cytoskeleton arrangement and indicators of programmed cell death may help clarify the processes involved during the ontogeny of that gland. The goal of our study was to analyze subcellular changes during schizogenous formation and secretion production and release into the lumen in resin ducts of Kielmeyera appariciana. Our results demonstrate the participation of pectinase through the loosening of the central cells of the rosette, which subsequently split from each other through polarized growth mediated by a rearrangement of the microtubules. The resin is mainly synthesized in plastids and endoplasmic reticulum and is observed inside vesicles and small vacuoles. The secretion release is holocrine and occurs through programmed cell death related to the release of reactive oxygen species, causing cytoplasm darkening, chromatin condensation, vacuole rupture and plastid and mitochondria degeneration. Cellulase activity was identified prior to the rupture of the cell wall, causing the release of secretion into the lumen of the duct. The participation of the cytoskeleton was observed for the first time during schizogeny of ducts as well as programmed cell death as part of the process of the release of holocrine secretion. This type of secretion release may be a key innovation in Kielmeyera since it has not been observed in ducts of any other plant thus far.

RESUMO

The characterization of colleters in Rubiaceae is crucial for understanding their role in plant function. Analyzing colleters in Palicourea tetraphylla and Palicourea rudgeoides aims to deepen the understanding of these structures morphoanatomical and functional characteristics. The study reveals colleters with palisade epidermis and a parenchymatic central axis, classified as standard type, featuring vascularization and crystals. Colleter secretion, abundant in acidic mucopolysaccharides, proteins, and phenolic compounds, protects against desiccation. The ontogenesis, development, and senescence of the colleters are quite rapid and fulfill their role well in biotic and abiotic protection because these structures are present at different stages of development in the same stipule. Pronounced protrusions on the colleters surface, coupled with the accumulation of secretion in the intercellular and subcuticular spaces, suggest that the secretory process occurs through the wall, driven by pressure resulting from the accumulation of secretion. The microorganisms in the colleters' secretion, especially in microbiota-rich environments such as the Atlantic Forest, provide valuable information about plant-microorganism interactions, such as resistance to other pathogens and organisms and ecological balance. This enhanced understanding of colleters contributes to the role of these structures in the plant and enriches knowledge about biological interactions within specific ecosystems and the family taxonomy.

RESUMO

Thermal variations due to global climate change are expected to modify the distributions of marine ectotherms, with potential pathogen translocations. This is of particular concern at high latitudes where cold-adapted stenothermal fish such as the Notothenioids occur. However, little is known about the combined effects of thermal fluctuations and immune challenges on the balance between cell damage and repair processes in these fish. The aim of this study was to determine the effect of thermal variation on specific genes involved in the ubiquitination and apoptosis pathways in two congeneric Notothenioid species, subjected to simulated bacterial and viral infections. Adult fish of Harpagifer bispinis and Harpagifer antarcticus were collected from Punta Arenas (Chile) and King George Island (Antarctica), respectively, and distributed as follows: injected with PBS (control), LPS (2.5 mg/kg) or Poly I:C (2 mg/kg) and then submitted to 2, 5 and 8 °C. After 1 week, samples of gills, liver and spleen were taken to evaluate the expression by real-time PCR of specific genes involved in ubiquitination (E3-ligase enzyme) and apoptosis (BAX and SMAC/DIABLO). Gene expression was tissue-dependent and increased with increasing temperature in the gills and liver while showing an opposite pattern in the spleen. Studying a pair of sister species that occur across the Antarctic Polar Front can help us understand the particular pressures of intertidal lifestyles and the effect of temperature in combination with biological stressors on cell damage and repair capacity in a changing environment.

Assuntos

RESUMO

OBJECTIVES: Comprehensive cross-interaction of multiple programmed cell death (PCD) patterns in the patients with lung adenocarcinoma (LUAD) have not yet been thoroughly investigated. METHODS: Here, we collected 19 different PCD patterns, including 1911 PCD-related genes, and developed an immune-derived multiple programmed cell death index (MPCDI) based on machine learning methods. RESULTS: Using the median MPCDI scores, we categorized the LUAD patients into two groups: low-MPCDI and high-MPCDI. Our analysis of the TCGA-LUAD training cohort and three external GEO cohorts (GSE37745, GSE30219, and GSE68465) revealed that patients with high-MPCDI experienced a more unfavorable prognosis, whereas those with low-MPCDI had a better prognosis. Furthermore, the results of both univariate and multivariate Cox regression analyses further confirmed that MPCDI serves as a novel independent risk factor. By combining clinical characteristics with the MPCDI, we constructed a nomogram that provides an accurate and reliable quantitative tool for personalized clinical management of LUAD patients. The findings obtained from the analysis of C-index and the decision curve revealed that the nomogram outperformed various clinical variables in terms of net clinical benefit. Encouragingly, the low-MPCDI patients are more sensitive to commonly used chemotherapy drugs, which suggests that MPCDI scores have a guiding role in chemotherapy for LUAD patients. CONCLUSION: Therefore, MPCDI can be used as a novel clinical diagnostic classifier, providing valuable insights into the clinical management and clinical decision-making for LUAD patients.

Assuntos

RESUMO

INTRODUCTION AND OBJECTIVES: Acute liver injury (ALI) is characterized by massive hepatocyte death with high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the physiopathological processes of ALI, which can damage mitochondria and release NLRP3 inflammasome particles, causing systemic inflammatory responses. Z-DNA Binding Protein 1 (ZBP1) is a sensor that induces cell death. Here, we investigated whether ZBP1 participates in hepatocyte pyroptosis and explored the possible pathogenesis of ALI. MATERIALS AND METHODS: Hepatocyte pyrotosis was induced with lipopolysaccharide (LPS) and nigericin (Nig), and the expression of Zbp1 (ZBP1) was examined by western blot analysis and RT-qPCR. Further, we transfected AML-12 (LO2 and HepG2) cell lines with Zbp1 (ZBP1) siRNA. After ZBP1 was silenced, LDH release and flow cytometry were used to measure the cell death; Western blot analysis and RT-qPCR were used to detect the marker of NLRP3 inflammasome activation and pyroptosis. We also detected the expression of mitochondrial linear rupture marker phosphoglycerate mutase family member 5 (PGAM5) using western blot analysis and reactive oxygen species (ROS) using the DCFH-DA method. RESULTS: The expression of ZBP1 was up-regulated in LPS/Nig-induced hepatocytes. Si-Zbp1 (Si-ZBP1) inhibited NLRP3 inflammasome activation and pyroptosis in LPS/Nig-induced hepatocytes. Moreover, ZBP1 silencing inhibited the expression of PGAM5 by reducing ROS production. CONCLUSIONS: ZBP1 promotes hepatocellular pyroptosis by modulating mitochondrial damage, which facilitates the extracellular release of ROS.

Assuntos

RESUMO

Natural killer/T-cell lymphoma (NK/T-cellL) is an aggressive non-Hodgkin's lymphoma with limited treatment options for patients who experience disease progression or recurrence after second-line treatment. The use of new therapies, such as pembrolizumab, which involves immune checkpoint blockade mechanisms, is proposed. This systematic review followed the MOSE guidelines and searched PUBMED/MEDLINE, EMBASE, and Scopus databases. Fourteen articles were found, reporting on the use of pembrolizumab anti PD-1 in NK/T-cellL patients. The objective response rate was 84.50%, with disease-free survival ranging from two to 48 months. The complete response rate was 61.6%, and the quality of the reported studies was evaluated to be of high and moderate confidence bias levels in case reports and high bias in clinical trials. Pembrolizumab and others anti PD-1 are treatment options for refractory/recurrent NK/T-cellL, regardless of PD-L1 expression, with good short- and long-term results and low adverse events.

Assuntos

RESUMO

BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.

RESUMO

ABSTRACT Objective Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. Methods This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. Results A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. Conclusions PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.

RESUMO

Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6th decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3ß and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction. OBJECTIVE: To investigate the protein expression of PD-L1 and GSK-3ß and the CD8-positive immune infiltrates in bladder carcinomas. MATERIALS AND METHODS: This was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3ß (27C10), CD8 (7103ß) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured. RESULTS: The immunoexpression of GSK-3ß (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3ß and PD-L1 (P = 0.033), and CD8 and PD-L1 (P<0.002) showed significant correlations. No significant associations were observed between GSK-3ß and CD8. The positivity of GSK-3ß and PD-L1 was predominant in high-grade tumors. CONCLUSION: Despite the tumor microenvironment heterogeneity, the expression of CD8, GSK-3ß and PDL1 could be valuable and GSK-3ß could be a potential target in advanced bladder cancer, especially in the context of immunotherapy.

RESUMO

Araceae comprises a diverse group of plants that grow in various habitats, ranging from submerged aquatics to lithophytes. Thus, aroids are likely to show diverse glands acting in several plant-environment interactions, including colleters that protect young shoots. Based on this premise and the lack of studies regarding secretory structures in Araceae, we employed standard light and electron microscopy methods to test the hypothesis that colleters are present in Anthurium. Our main goals were to identify mucilage glands in A. andraeanum by conducting a detailed anatomical study of their structure, ultrastructure, and secretory activity. We found finger-like colleters in the apex of young leaves, spathes, and unexpanded cataphylls as well as secreting zones at the apex of expanded cataphylls, at the margins of non-fused cataphylls, and throughout the keels in two-keeled cataphylls. The colleters develop precociously and senesce shortly afterwards. Ultrastructural data and histochemistry confirmed the production of a polysaccharide-rich secretion that fills the spaces within the developing shoot. As far we know, this is the first time that colleters have been reported for Araceae. The functional roles of the secretion and the position of finger-like colleters concerning the 'precursor tip' of monocotyledons are discussed. Future research correlating secretory activity in colleters of species from different habitats might reveal a great diversity of mucilage glands with ecological and evolutionary significance to the family.

RESUMO

Background and Objective: Immune checkpoint inhibition has shed light on a new era in cancer therapy, and randomized clinical trials have demonstrated that a meaningful portion of the overall population of metastatic gastric cancer (GC) patients may derive clinical benefit from immunotherapy, which raises the relevance in identifying predictive biomarkers. Programmed cell death-ligand 1 (PD-L1) expression has demonstrated a significant association between level of expression and the magnitude of benefit derived from immune checkpoint inhibition in GC. Nevertheless, this biomarker shows several pitfalls that must be considered in the therapeutic decision to incorporate immune checkpoint inhibition as the standard of care of GC, such as spatial and temporal heterogeneity, interobserver variability, immunohistochemistry (IHC) assay, and influence by chemotherapy or radiation therapy. Methods: In the present comprehensive review, we revised the main studies regarding PD-L1 evaluation in GC. Key Content and Findings: Here we describe the molecular characteristics of the tumor microenvironment in GC, the obstacles in the interpretation of PD-L1 expression and present the data of the clinical trials that have evaluated the efficacy and safety of immune checkpoint inhibition and the association with the biomarker expression, both in first-line and later lines of therapy. Conclusions: From the emerging predictive biomarkers for immune checkpoint inhibition, PD-L1 has demonstrated a meaningful association between level of expression in tumor microenvironment and the magnitude of benefit derived from immune checkpoint inhibition in GC.

RESUMO

PURPOSE: Doramectin (DRM) is a kind of avermectin drugs, and it has been shown that DRM has anti-cancer effects. However, the molecular mechanism of DRM in programmed cell death (PCD) aspects is still unclear. The objective of this study was to confirm whether DRM induced PCD in glioma cells. METHODS: In this experiment, the MTT assay and Ki-67 assay were used to detect in vitro cell viability and in vivo tumor proliferation. Then, the effect of DRM on PCD was analyzed by transcriptome comparison. Next, Endogenous apoptosis was detected by transmission electron microscopy (TEM), the DNA gel electrophoresis, JC-1 assay, western blotting and qRT-PCR. Meanwhile, necroptosis was detected by TEM, Hoechst 33342, FITC and PI staining assay, western blotting. RESULTS: We found DRM induced apoptosis through Bcl-2/Bax/Caspase-3 pathway. And, DRM induced ROS overproduction, then ROS caused necroptosis through RIPK1/RIPK3/MLKL pathway, Mitochondria acted as a bridge between the two pathways. CONCLUSION: Our research provided new insight with the function of anti-cancer of DRM. These results demonstrated DRM may be used as potential therapeutic agents inducing apoptosis and necroptosis for cancer therapy.

Assuntos

RESUMO

Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

Assuntos

RESUMO

The chemical diversity of sphingolipids in plants allows the assignment of specific roles to special molecular species. These roles include NaCl receptors for glycosylinositolphosphoceramides or second messengers for long-chain bases (LCBs), free or in their acylated forms. Such signaling function has been associated with plant immunity, with an apparent connection to mitogen-activated protein kinase 6 (MPK6) and reactive oxygen species (ROS). This work used in planta assays with mutants and fumonisin B1 (FB1) to generate varying levels of endogenous sphingolipids. This was complemented with in planta pathogenicity tests using virulent and avirulent Pseudomonas syringae strains. Our results indicate that the surge of specific free LCBs and ceramides induced by FB1 or an avirulent strain trigger a biphasic ROS production. The first transient phase is partially produced by NADPH oxidase, and the second is sustained and is related to programmed cell death. MPK6 acts downstream of LCB buildup and upstream of late ROS and is required to selectively inhibit the growth of the avirulent but not the virulent strain. Altogether, these results provide evidence that a LCB- MPK6- ROS signaling pathway contributes differentially to the two forms of immunity described in plants, upregulating the defense scheme of a non-compatible interaction.

Assuntos

RESUMO

BACKGROUND AND OBJECTIVE: This study intended to evaluate the prognostic effects of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in survival and their associations with clinicopathological characteristics in patients with gastric cancer. METHODS: PubMed, Scopus, ProQuest, Web of Science, and Ovid databases were searched to obtain the relevant studies. Eleven studies with 2298 patients were included in this study. RESULTS: Like the level of TILs, there were no significant associations between PD-L1 expression and TNM stage, lymph node metastasis, vascular invasion, and tumor location (All p values ≥ 0.05). Furthermore, there was no significant association between PD-L1 expression with overall survival (OS) (HR = 0.76, 95% CI: 0.55 to 1.05, p value = 0.10) and disease-free survival (DFS) (HR = 0.62, 95% CI: 0.10 to 3.68, p value = 0.59). In the assessment of TILs presence and survival association, the analysis showed no association between TILs presence and overall survival (OS) (HR = 0.95, 95% CI: 0.62 to 1.45). CONCLUSIONS: In conclusion, the study has revealed no prognostic effect of PD-L1 and TILs in gastric cancer patients.

Assuntos

RESUMO

PURPOSE: Small cell lung cancer (SCLC) is a heterogeneous malignancy with genetic and phenotypic disparity. However, the association between intratumor heterogeneity (ITH) and immunological features as well as the impact of ITH on prognosis has never been explored in SCLC. Hence, we investigated the relationship between ITH and their immunological features and explored the effect of ITH on overall survival (OS) in patients with SCLC. METHODS: Programmed cell death-ligand 1 (PD-L1), CD8+ cell infiltration was calculated through immunohistochemical staining and tumor mutational burden (TMB), tumor neoantigen burden (TNB), and ITH levels via whole-exome sequencing (WES). RESULTS: Significant correlation was not found in ITH versus TMB, ITH versus TNB (P = 0.1821, P = 0.0612). No significant variation in ITH was found between negative PD-L1 SCLC patients and positive PD-L1 ones (P = 0.0610 for TPS, P = 0.6347 for CPS). Interestingly, we demonstrated the negative correlation between CD8+ T cell infiltration and ITH (P = 0.0220). More importantly, significant OS benefit was detected in ITH-low SCLC patients in comparison with ITH-high ones (P = 0.0049). ITH was an independent prognostic factor on OS with clinicopathological variables adjusted (HR, 2.044; 95% CI 1.190-3.512; P = 0.010). We also demonstrated significantly different driver genes and CNV between ITH-low and ITH-high SCLC. CONCLUSION: Our work pointed the negative association of ITH with CD8+ T cell infiltration and suggested ITH as a potential predictor of OS in SCLC, putting forward a direction for more precise and individualized therapeutic strategies for SCLC.

Assuntos

RESUMO

Chromoblastomycosis (CBM) is a chronic, progressive fungal disease of the skin and subcutaneous tissue caused by a group of dematiaceous fungi. Verrucous lesions present parasite-rich granulomas and predominance of a Th2 patterns of cytokines. The inflammasome constitutes a macromolecular protein complex that play a role in the activation of caspase 1 that cleaves pro-IL1ß and pro-IL18, essential mediators of inflammation, and also activates pyroptosis. We intended to explore the presence and a possible role of inflammasome elements in cutaneous human lesions in CBM, considering the expression of IL1ß, IL18, caspase 1, NLRP1, and also RIPK3, a key downstream component of necroptosis signaling. 35 skin biopsies of cutaneous lesions of verrucous form of CBM and 10 biopsies from normal skin were selected. The diagnosis was based on histological and clinical analysis. An immunohistochemical protocol was performed. The histopathological analysis evidenced epidermis with hyperkeratosis, irregular acanthosis, and micro abscesses. The dermis presented suppurative granulomas and inflammatory infiltrate composed by giant cells, macrophages, epithelioid cells, lymphocytes, and some eosinophils. Positive cells were distributed in the inflammatory infiltrate, with an increased number of cells expressing caspase 1, IL1ß and IL18. Cells expressing RIPK3 and NLRP1 were less frequent. The intense presence of caspase 1, IL1ß and IL18, allied to NLRP1 expression, suggest that inflammasome and pyroptosis could play a role in the immune response against fungal agents of CBM. Our results, allied to data from literature, could suggest that inflammasome-mediated response and pyroptosis could be a target to be explored to decrease CBM lesions.

Assuntos

RESUMO

Abstract Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

RESUMO

Introducción:La inmunoterapia con pembrolizumab ha mejorado el pronóstico del cáncer de pulmón metastásico. En el presente caso se presenta la supervivencia extendidad y evolución de un paciente específico.Caso clínico:Hombre de 66 años, fumador. Diagnosticado de masa pulmonar en lóbulo infe-rior izquierdo de dimensiones 9 x 8 cm, con metástasis supra e infratentoriales intraaxiliares. Taller diagnóstico: Establecida como neoplasia de pulmón en estadio IVc, se comprobó el estado de PDL1 que positivo en un 80 % de la muestra de masa pulmonar. Debuta con me-tástasis cerebrales.Evolución: Se inció inmunoterapia con Pembrolizumab, el cual se mantubo hasta la presencia de un efecto secundario atribuido al pembrolizumab, cumpliendo 30meses de supervivencia hasta el cierre de esta observación no se reportó la muerte del paciente.Conclusiones:En el presente reporte, la determinación del biomarcador histológico PDL1 po-sitivo en cáncer de pulmón ayudo a prescribir un tratamiento con inmunoterpia dirigida, lo que demostró aumentar la supervivencia más allá que el tratamiento convencional con quimiote-rapia

Introduction: Immunotherapy with pembrolizumab has improved the prognosis of metastatic lung cancer. A specific patient's extended survival and evolution is presented in the present case.Clinical case: 66-year-old man, smoker. Diagnosed with a lung mass in the left lower lobe measuring 9 x 8 cm, with supra and infratentorial intra-axial metastases.Diagnostic workshop: To establisha stage IVc lung neoplasm, 80% of the lung mass sample was confirmed to be positive for PDL1.Evolution: Immunotherapy was started with Pembrolizumab, which was maintained until the presence of a side effect attributed to pembrolizumab, completing 30 months of survival until the closure of this observation, the patient's death was not reported.Conclusions: In the present report, the determination of the positive histological biomarker PDL1 in lung cancer helped prescribe treatment with targeted immunotherapy, which was shown to increase survival beyond conventional treatment with chemotherapy

Assuntos