RESUMEN
INTRODUCTION: Despite screening, the incidence of breast cancer is increasing worldwide. Neoadjuvant chemotherapy (NAC) response is one of the most important parameters taken into consideration in surgery, optimal adjuvant chemotherapy planning and prognosis prediction. Research on predictive markers for the response to NAC is still ongoing. In our study, we investigated the relationship between tumor-infiltrating neutrophils/mast cells/lymphocytes and NAC response in breast carcinomas. MATERIAL AND METHOD: Study included 117 patients who were diagnosed with invasive breast carcinoma using core needle biopsy. In these biopsies tumor-infiltrating neutrophils/mast cells/lymphocytes were evaluated and Miller Payne Score was used for NAC response. RESULT: 53 patients exhibited high TILs, 36 had high TINs, and 46 showed high TIMs. While pathological complete response was 27 % in all patients, it was 38 % in high TINs patients, 35 % in high TILs patients, and 28 % in high TIMs patients. High TIMs were observed to be statistically associated with survival. TILs, TINs, nuclear grade, ER, PR and HER2 expression, Ki-67 proliferation index were found to be associated with the Miller - Payne score. In multivariate analysis, TINs, nuclear grade, pathological stage, and molecular subtype were found to be independent risk factors for treatment response. CONCLUSION: TINs have better prognostic value to predict neoadjuvant treatment than TILs. High TIMs are associated with increased overall survival. The inclusion of TINs in NAC response and TIMs in overall survival in pathology reports and treatment planning is promising in breast carcinomas as they are simple to use and reproducible markers.
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Neoplasias de la Mama , Linfocitos Infiltrantes de Tumor , Terapia Neoadyuvante , Neutrófilos , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Femenino , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Adulto , Linfocitos Infiltrantes de Tumor/inmunología , Neutrófilos/patología , Neutrófilos/metabolismo , Anciano , Pronóstico , Quimioterapia Adyuvante/métodos , Linfocitos/patología , Linfocitos/metabolismoRESUMEN
Mast cells (MCs), powerful immune cells that heavily infiltrate cancer cells, play a crucial role in tumor formation. Activated MCs can release histamine and a family of proteases through degranulation effects, concurrently achieving endothelial junction weakening and stromal degradation of the tumor microenvironment, thereby clearing the obstacles for nano-drug infiltration. To achieve precise activation of tumor-infiltrating MCs, orthogonally excited rare earth nanoparticles (ORENP), with two channels, are introduced for the controllable stimulating drugs release wrapped in "photocut tape". The ORENP can emit near-infrared II (NIR-II) for image tracing for tumor localization in Channel 1 (808/NIR-II) and allows energy upconversion to emit ultraviolet (UV) light for releasing drugs for MCs stimulation in Channel 2 (980/UV). Finally, the combined use of chemical and cellular tools enables clinical nano-drugs to achieve a significant increase in tumor infiltration, thereby enhancing the efficacy of nano-chemotherapy.
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Nanopartículas , Neoplasias , Humanos , Mastocitos , Neoplasias/patología , Rayos Ultravioleta , Nanopartículas/uso terapéutico , Microambiente TumoralRESUMEN
Objective: The purpose of this study was to explore the composition of tumor-infiltrating immune cells (TIIC) and prognostic significance of tumor-infiltrating mast cells (TIMC) in adrenocortical carcinoma (ACC). Methods: The gene expression profiles of ACC were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE90713, GSE12368). The abundance of TIICs in ACC samples was calculated by CIBERSORT algorithm and immunohistochemistry was used to identify mast cells of 39 tumor samples from Fudan University Shanghai Cancer Center (FUSCC). Differentially expressed genes (DEGs) were analyzed by LIMMA package using R software. Survival analysis was analyzed by Kaplan-Meier method and Cox regression models. Results: The abundance of mast cells (p = .008) was positively correlated with ACC patients' outcome in TCGA cohort and was also positively correlated with both overall survival (p < .05) and progression-free survival (p < .05) in FUSCC cohort. Different TIMC infiltrations showed significant changes in signaling pathways including DNA replication, nuclear chromosome segregation, and meiotic cell cycle process of ACC. In addition, elevated expression of eight hub genes (KIF18A, CDCA8, SKA1, CEP55, BUB1, CDK1, SGOL1, SGOL2) related to the abundance of TIMC in ACC was significantly correlated with the poor prognosis of the patients. Conclusion: In conclusion, higher TIMC infiltration was positively correlated with ACC patients' outcome in both TCGA and FUSCC cohort. Lower TIMC infiltration and elevated expression of hub genes (KIF18A, CDCA8, SKA1, CEP55, BUB1, CDK1, SGOL1, SGOL2) are markedly correlated with aggressive progression and poor prognosis, which might shed lights on novel targets for treatment strategies.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Neoplasias de la Corteza Suprarrenal/genética , Carcinoma Corticosuprarrenal/genética , Proteínas de Ciclo Celular , China , Proteínas Cromosómicas no Histona , Biología Computacional , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Cinesinas , Masculino , Mastocitos , PronósticoRESUMEN
Recent studies have reported that tumor-infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine-based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine-based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM-activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell-related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine-based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.
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Neoplasias de la Vesícula Biliar/patología , Linfocitos Infiltrantes de Tumor/patología , Mastocitos/patología , Antimetabolitos Antineoplásicos/uso terapéutico , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Quimioterapia Adyuvante/métodos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/metabolismo , Humanos , Interferón gamma/metabolismo , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Persona de Mediana Edad , Pronóstico , Transducción de Señal/efectos de los fármacos , GemcitabinaRESUMEN
PURPOSE: Hypoxia-inducible factor 2α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mechanisms. EXPERIMENTAL DESIGN: We immunohistochemically evaluated immune cells infiltrations and prognostic value of HIF-2α expression in a retrospective Zhongshan Hospital cohort of 280 ccRCC patients. Fresh tumor samples, non-tumor tissues and autologous peripheral blood for RT-PCR, ELISA and flow cytometry analyses were collected from patients who underwent nephrectomy in Zhongshan Hospital from September 2017 to April 2018. The TCGA KIRC cohort and SATO cohort were assessed to support our findings. RESULTS: We demonstrated that ccRCC patients with HIF-2αhigh tumors exhibited reduced overall survival (p = 0.025) and recurrence-free survival (p < 0.001). Functions of CD8+ T cells were impaired in HIF-2αhigh patients. In ccRCC patients, HIF-2α induced the expression of stem cell factor (SCF), which served as chemoattractant for mast cells. Tumor infiltrating mast cells impaired anti-tumor immunity partly by secreting IL-10 and TGF-ß. HIF-2α mRNA level adversely associated with immunostimulatory genes expression in KIRC and SATO cohorts. CONCLUSIONS: HIF-2α contributed to evasion of anti-tumor immunity via SCF secretion and subsequent recruitment of mast cells in ccRCC patients.