RESUMEN

Marine mollusk production is increasing worldwide, and this trend is being evidenced in South American countries, where several species of bivalves are produced, exploited, and traded. This activity brings benefits either for the ecosystem, as it is a less impactful and polluting than other aquaculture practices, and to coastal human communities, as it provides food and income. However, emergence of outbreaks by pathogens is a major concern and can put an entire developing sector at risk. Perkinsosis is a disease caused by Perkinsus spp. protozoans that affect mollusks worldwide. In this review we provide information on Perkinsus spp. among bivalves from South America. Infections by these parasites were only reported to date among coastal Atlantic bivalves of Argentina, Uruguay, and Brazil. The vast majority of cases and studies are reported from Brazil. We comprehensively review those results here. Finally, we suggest some considerations for future investigations that may expand our knowledge of these parasites.

Asunto(s)

Alveolados , Animales , América del Sur/epidemiología , Bivalvos/parasitología

RESUMEN

BACKGROUND: Region-specific immune environments in the epididymis influence the immune responses to uropathogenic Escherichia coli (UPEC) infection, a relevant cause of epididymitis in men. Toll-like receptors (TLRs) are essential to orchestrate immune responses against bacterial infections. The epididymis displays region-specific inflammatory responses to bacterial-derived TLR agonists, such as lipopolysaccharide (LPS; TLR4 agonist) and lipoteichoic acid (LTA; TLR2/TLR6 agonist), suggesting that TLR-associated signaling pathways could influence the magnitude of inflammatory responses in epididymitis. OBJECTIVES: To investigate the expression and regulation of key genes associated with TLR4 and TLR2/TLR6 signaling pathways during epididymitis induced by UPEC, LPS, and LTA in mice. MATERIAL AND METHODS: Epididymitis was induced in mice using UPEC, ultrapure LPS, or LTA, injected into the interstitial space of the initial segment or the lumen of the vas deferens close to the cauda epididymidis. Samples were harvested after 1, 5, and 10 days for UPEC-treated animals and 6 and 24 h for LPS-/LTA-treated animals. Ex vivo epididymitis was induced by incubating epididymal regions from naive mice with LPS or LTA. RT-qPCR and Western blot assays were conducted. RESULTS: UPEC infection up-regulated Tlr2, Tlr4, and Tlr6 transcripts and their associated signaling molecules Cd14, Ticam1, and Traf6 in the cauda epididymidis but not in the initial segment. In these epididymal regions, LPS and LTA differentially modulated Tlr2, Tlr4, Tlr6, Cd14, Myd88, Ticam1, Traf3, and Traf6 expression levels. NFKB and AP1 activation was required for LPS- and LTA-induced up-regulation of TLR-associated signaling transcripts in the cauda epididymidis and initial segment, respectively. CONCLUSION: The dynamic modulation of TLR4 and TLR2/TLR6 signaling pathways gene expression during epididymitis indicates bacterial-derived antigens elicit an increased tissue sensitivity to combat microbial infection in a spatial manner in the epididymis. Differential activation of TLR-associated signaling pathways may contribute to fine-tuning inflammatory responses along the epididymis.

Asunto(s)

Epididimitis , Lipopolisacáridos , Transducción de Señal , Ácidos Teicoicos , Receptor Toll-Like 2 , Receptor Toll-Like 4 , Animales , Masculino , Epididimitis/genética , Epididimitis/metabolismo , Epididimitis/microbiología , Ratones , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Ácidos Teicoicos/farmacología , Escherichia coli Uropatógena , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/genética , Receptor Toll-Like 6/genética , Receptor Toll-Like 6/metabolismo , Epidídimo/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Ratones Endogámicos C57BL , Enfermedad Aguda

Asunto(s)

Microbiota , Neoplasias , Humanos , Neoplasias/terapia , Sistema Inmunológico , Inmunoterapia

RESUMEN

Obesity alters the capacity of effective immune responses in infections. To further address this phenomenon in the context of COVID-19, this study investigated how the immunophenotype of leukocytes was altered in individuals with obesity in severe COVID-19. This cross-sectional study enrolled 27 ICU COVID-19 patients (67% women, 56.33 ± 19.55 years) that were assigned to obese (BMI ≥ 30 kg/m2, n = 9) or non-obese (BMI < 30kg/m2, n = 18) groups. Monocytes, NK, and both Low-Density (LD) and High-Density (HD) neutrophils were isolated from peripheral blood samples, and surface receptors' frequency and expression patterns were analyzed by flow cytometry. Clinical status and biochemical data were additionally evaluated. The frequency of monocytes was negatively correlated with BMI, while NK cells and HD neutrophils were positively associated (p < 0.05). Patients with obesity showed a significant reduction of monocytes, and these cells expressed high levels of PD-L1 (p < 0.05). A higher frequency of NK cells and increased expression of TREM-1+ on HD neutrophils were detected in obese patients (p < 0.05). The expression of receptors related to antigen-presentation, phagocytosis, chemotaxis, inflammation and suppression were strongly correlated with clinical markers only in obese patients (p < 0.05). Collectively, these outcomes revealed that obesity differentially affected, and largely depressed, innate immune response in severe COVID-19.

RESUMEN

The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study was performed with 112 HIV-uninfected and 41 HIV-infected nonindigenous women. Anal and cervical scrapings were collected and analyzed for HPV, Chlamydia trachomatis (CT), Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2). The Kappa test evaluated the concordance between anal and genital infections. The overall prevalence of anal HPV infection was 31.3% in HIV-uninfected and 97.6% in HIV-infected women. The most frequent anal high-risk HPV (hrHPV) types were HPV18 and HPV16 in HIV-uninfected women and HPV51, HPV59, HPV31, and HPV58 in HIV-infected women. Anal HPV75 Betapapillomavirus was also identified. Anal non-HPV STIs were identified in 13.0% of all participants. The concordance analysis was fair for CT, MG, and HSV-2, almost perfect agreement for NG, moderate for HPV, and variable for the most frequent anal hrHPV types. Thus, a high prevalence of anal HPV infection with moderate and fair concordance between anal and genital HPV and non-HPV STIs was observed in our study.

Asunto(s)

Infecciones por Chlamydia , Infecciones por VIH , Infecciones por Papillomavirus , Enfermedades de Transmisión Sexual , Humanos , Femenino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Brasil/epidemiología , Estudios Transversales , Enfermedades de Transmisión Sexual/complicaciones , Enfermedades de Transmisión Sexual/epidemiología , Chlamydia trachomatis , Cuello del Útero , Neisseria gonorrhoeae , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Prevalencia , Infecciones por Chlamydia/complicaciones , Infecciones por Chlamydia/epidemiología

RESUMEN

Naegleria fowleri is an etiological agent that generates primary amoebic meningoencephalitis; unfortunately, no effective treatment or vaccine is available. The objective of this work was to determine the immunoprotective response of two vaccine antigens, as follows: (i) the polypeptide band of 19 kDa or (ii) a predicted immunogenic peptide from the membrane protein MP2CL5 (Smp145). Both antigens were administered intranasally in mice using cholera toxin (CT) as an adjuvant. The survival rate and immune response of immunized mice with both antigens and challenged with N. fowleri trophozoites were measured in the nose-associated lymphoid tissue (NALT) and nasal passages (NPs) by flow cytometry and enzyme-linked immunosorbent assay (ELISA). We also determined the immunolocalization of both antigens in N. fowleri trophozoites by confocal microscopy. Immunization with the polypeptide band of 19 kDa alone or coadministered with CT was able to confer 80% and 100% of protection, respectively. The immunization with both antigens (alone or coadministered with CT) showed an increase in T and B lymphocytes. In addition, there was an increase in the expression of integrin α4ß1 and IgA in the nasal cavity of protected mice, and the IgA, IgG, and IgM levels were increased in serum and nasal washes. The immunolocalization of both antigens in N. fowleri trophozoites was observed in the plasma membrane, specifically in pseudopod-like structures. The MP2CL5 antigens evaluated in this work were capable of conferring protection which would lead us to consider them as potential candidates for vaccines against meningitis caused by N. fowleri.

Asunto(s)

Meningitis , Naegleria fowleri , Vacunas , Animales , Ratones , Toxina del Cólera , Inmunidad , Inmunoglobulina A

RESUMEN

Chronic kidney disease (CKD) patients have an increased risk of morbidity and mortality following SARS-CoV-2 infection. Vaccination in these patients is prioritized, and monitoring of the immune response is paramount to define further vaccination strategies. This prospective study included a cohort of 100 adult CKD patients: 48 with kidney transplant (KT) and 52 on hemodialysis without prior COVID-19. The patients were assessed for humoral and cellular immune responses after four months of an anti-SARS-CoV-2 primary two-dose vaccination scheme (CoronaVac or BNT162b2) and one month after a booster third dose of BNT162b2 vaccine. We identified poor cellular and humoral immune responses in the CKD patients after a primary vaccination scheme, and these responses were improved by a booster. Robust polyfunctional CD4+ T cell responses were observed in the KT patients after a booster, and this could be attributed to a higher proportion of the patients having been vaccinated with homologous BNT162b2 schemes. However, even after the booster, the KT patients exhibited lower neutralizing antibodies, attributable to specific immunosuppressive treatments. Four patients suffered severe COVID-19 despite three-dose vaccination, and all had low polyfunctional T-cell responses, underscoring the importance of this functional subset in viral protection. In conclusion, a booster dose of SARS-CoV-2 mRNA vaccine in CKD patients improves the impaired humoral and cellular immune responses observed after a primary vaccination scheme.

RESUMEN

PURPOSE: Protein extracts developed increased immunogenicity without the aid of adjuvants after gamma irradiation. Gamma irradiation of snake venom increased antivenin production by detoxification and enhanced immunity, probably due preferential uptake of irradiated venoms by macrophage scavenger receptors. We studied this uptake of irradiated soluble Toxoplasma gondii extract (STag) by the J774 macrophage cell line similar to antigen presenting cells. MATERIAL AND METHODS: We labeled STag by biosynthesis in living tachyzoites with radioactive amino acids before purification and irradiation or by adding labels as biotin or fluorescein in stored STag, for quantitative studies or subcellular distribution visualization. RESULTS: There was enhanced binding and uptake of irradiated STag into the cells compared to non-irradiated STag. Using fluorescein labeled antigens and morphological assays, we confirmed that cells avidly ingested both native and irradiated proteins but native STag were digested after ingestion while irradiated proteins remained in the cell, suggesting diverse intracytoplasmic pathways. Native or irradiated STag present the same in vitro sensitivity to three types of peptidases. Inhibitors of scavenger receptors (SRs) such as Dextran sulfate (SR-A1 blocker) or Probucol (SR-B blocker) affect the specific uptake of irradiated antigens, suggesting its association with enhanced immunity. CONCLUSIONS: Our data suggests that cell SRs recognize irradiated proteins, mainly SRs for oxidized proteins, leading to antigen uptake by an intracytoplasmic pathway with fewer peptidases that prolongs presentation to nascent major histocompatibility complex I or II and enhances immunity by better antigen presentation.

Asunto(s)

Macrófagos , Toxoplasma , Receptores Depuradores , Línea Celular , Toxoplasma/efectos de la radiación , Péptido Hidrolasas , Fluoresceínas

RESUMEN

RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses.

Asunto(s)

Infecciones por Coronavirus , Coronavirus , Infecciones por Enterovirus , Metapneumovirus , Virus Sincitial Respiratorio Humano , Humanos , ARN

RESUMEN

Objective: To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response. Methods: Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Results: Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17-39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Conclusions: Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.

Asunto(s)

COVID-19 , SARS-CoV-2 , Humanos , Femenino , Masculino , Adolescente , Adulto Joven , Adulto , Anticuerpos Antivirales , Inmunoglobulina G , Brasil/epidemiología , Inmunoglobulina M , Inmunoglobulina A , Inmunoglobulina E

RESUMEN

O objetivo deste trabalho foifornecer uma visão geral dos mecanismos inflamatórios envolvidos no processo da obesidade, com enfoque nas respostas imunes pró-inflamatórias e no papel das adipocinas nas reações inflamatórias, em humanos e animais, bem como a correlação com a espécie felina. A obesidade é considerada uma doença endócrina cada vez mais prevalente na espécie felina, causada por uma desordem nutricional de balanço energético negativo. É definida como um acúmulo excessivo de tecido adiposo que afeta negativamente a saúde do animal e está associada à diminuição da expectativa de vida, sendo que as causas que a desencadeiam são multifatoriais, sendo atreladas a diversos fatores genéticos e ambientais. O tecido adiposo é um órgão endócrino que participa ativamente do metabolismo energético e concentra fatores hormonais que são secretados pelos adipócitos, os quais modulam o metabolismo e exercem capacidade de envolver diretamente as respostas imunes inatas e adaptativas por meio da atividade dos principais tipos celulares, incluindo adipócitos e macrófagos responsáveis pela ativação e liberação de citocinas que afetam a função fisiológica normal, influenciando no desenvolvimento da inflamação crônica. A produção alterada de adipocinas na obesidade tem sido envolvida na fisiopatologia de diversos grupos de doenças e tem sido relatada sua possível contribuição para o desenvolvimento de resistência insulínica e diabetes mellitus. Apesar do incompleto compreendimento dos fatores desencadeantes da inflamação no tecido adiposo de gatos, sugere-se que estejam envolvidos aspectos associados à disfunção mitocondrial, hipóxia ou, ainda, que estejam associados fatores intrínsecos do adipócito.

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This study aimed to provide an overview of the inflammatory mechanisms involved in the obesity process focusing on pro-inflammatory immune responses and the role of adipokines in inflammatory reactionsm in animals and humans, as well as the correlation with the feline specie. Obesity is considered an increasingly prevalent endocrine disease in feline species, caused by a nutritional disorder with negative energy balance. It is defined as an excessive accumulation of adipose tissue that negatively affects the animal's health and is associated with a decrease in life expectancy and as triggering causes are multifactorial, being linked to several genetic and environmental factors. Adipose tissue is an endocrine organ that actively participates in energy metabolism and concentrates hormonal factors that are secreted by adipocytes, which modulate metabolism and exert the ability to directly involve innate and adaptive immune responses through the activity of the main cell types, including adipocytes and macrophages responsible for the activation and release of cytokines that affect normal physiological function, influencing the development of chronic inflammation. The altered production of adipokines in obesity has been implicated in the pathophysiology of several groups of diseases and their possible contribution to the development of insulin resistance and diabetes mellitus. Despite the incomplete understanding of the triggering factors of inflammation in the adipose tissue of cats, it is suggested that aspects associated with mitochondrial dysfunction, hypoxia, or even intrinsic factors of the adipocyte are involved.

Asunto(s)

Animales , Gatos , Enfermedades de los Gatos/inmunología , Adipocitos , Inflamación/veterinaria , Obesidad/veterinaria

Asunto(s)

Infecciones por Arbovirus , Arbovirus , Flavivirus , Humanos

RESUMEN

Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p<0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes (Sneathia, Shuttleworthia, Prevotella, and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1ß, rho=0.56, p=0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p=0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition.

Asunto(s)

Alphapapillomavirus , Microbiota , Infecciones por Papillomavirus , Femenino , Humanos , Inmunidad Mucosa , Masculino , Microbiota/genética , Papillomaviridae/genética

RESUMEN

Currently, the only available vaccine against tuberculosis is Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary tuberculosis protection provided by the vaccine varies depending on the strain, the patient's age and the evaluated population. Although the adaptive immune responses induced by different BCG strains have been widely studied, little conclusive data is available regarding innate immune responses, especially in macrophages. Here, we aimed to characterize the innate immune responses of human THP-1-derived macrophages at the transcriptional level following a challenge with either the BCG Mexico (M.BCG) or Phipps (P.BCG) strains. After a brief in vitro characterization of the bacterial strains and the innate immune responses, including nitric oxide production and cytokine profiles, we analyzed the mRNA expression patterns and performed pathway enrichment analysis using RNA microarrays. Our results showed that multiple biological processes were enriched, especially those associated with innate inflammatory and antimicrobial responses, including tumor necrosis factor (TNF)-α, type I interferon (IFN-I) and IFN-γ. However, four DEGs were identified in macrophages infected with M.BCG compared to P. BCG. These findings indicated the proinflammatory stimulation of macrophages induced by both BCG strains, at the cytokine level and in terms of gene expression, suggesting a differential expression pattern of innate immune transcripts depending on the mycobacterial strain.

Asunto(s)

Vacuna BCG , Mycobacterium bovis , Citocinas/metabolismo , Humanos , Inmunidad Innata , Macrófagos/metabolismo , Fenotipo , ARN/metabolismo

RESUMEN

Chagas disease is caused by the protozoan Trypanosoma cruzi and is endemic to Central and South America. However, it has spread around the world and affects several million people. Treatment with currently available drugs cause several side effects and require long treatment times to eliminate the parasite, however, this does not improve the chronic effects of the disease such as cardiomyopathy. A therapeutic vaccine for Chagas disease may be able to prevent the disease and improve the chronic effects such as cardiomyopathy. This vaccine would be beneficial for both infected people and those which are at risk in endemic and non-endemic areas. In this article, we will review the surface antigens of T. cruzi, in order to choose those that are most antigenic and least variable, to design effective vaccines against the etiological agent of Chagas disease. Also, we discuss aspects of the design of nucleic acid-based vaccines, which have been developed and proven to be effective against the SARS-CoV-2 virus. The role of co-adjuvants and delivery carriers is also discussed. We present an example of a chimeric trivalent vaccine, based on experimental work, which can be used to design a vaccine against Chagas disease.

Asunto(s)

Enfermedad de Alzheimer , COVID-19 , Enfermedad de Alzheimer/diagnóstico , COVID-19/diagnóstico , Humanos , SARS-CoV-2

Asunto(s)

Susceptibilidad a Enfermedades/inmunología , Interacciones Huésped-Parásitos/inmunología , Tejido Nervioso/parasitología , Parásitos/fisiología , Tropismo , Animales , Humanos , Especificidad de Órganos/inmunología

RESUMEN

Powdery mildew causes substantial losses in crop and economic plant yields worldwide. Although powdery mildew infection of rubber trees (Hevea brasiliensis), caused by the biotrophic fungus Erysiphe quercicola, severely threatens natural rubber production, little is known about the mechanism by which E. quercicola adapts to H. brasiliensis to invade the host plant. In barley and Arabidopsis thaliana, lifeguard (LFG) proteins, which have topological similarity to BAX INHIBITOR-1, are involved in host plant susceptibility to powdery mildew infection. In this study, we characterized an H. brasiliensis LFG protein (HbLFG1) with a focus on its function in regulating defense against powdery mildew. HbLFG1 gene expression was found to be upregulated during E. quercicola infection. HbLFG1 showed conserved functions in cell death inhibition and membrane localization. Expression of HbLFG1 in Nicotiana benthamiana leaves and A. thaliana Col-0 was demonstrated to significantly suppress callose deposition induced by conserved pathogen-associated molecular patterns chitin and flg22. Furthermore, we found that overexpression of HbLFG1 in H. brasiliensis mesophyll protoplasts significantly suppressed the chitin-induced burst of reactive oxygen species. Although A. thaliana Col-0 and E. quercicola displayed an incompatible interaction, Col-0 transformants overexpressing HbLFG1 were shown to be susceptible to E. quercicola. Collectively, the findings of this study provide evidence that HbLFG1 acts as a negative regulator of plant immunity that facilitates E. quercicola infection in H. brasiliensis.

Asunto(s)

Hevea , Hevea/genética , Enfermedades de las Plantas , Inmunidad de la Planta

RESUMEN

Immunotherapy has changed the landscape of cancer treatment and has significantly improved the outcome of several cancer types including breast, lung, colorectal and prostate. Neoantigen recognition and immune checkpoint inhibitors are nowadays the milestones of different immunotherapeutic regimes; however, high cost, primary and acquired resistance and the high variability of responses make their extensive use difficult. The development of better predictive biomarkers that represent tumour diversity shows promise because there is a significant body of clinical data showing a spectrum of immunotherapeutic responses that might be related back to their specific characteristics. This article makes a conceptual and historical review to summarise the main advances in our understanding of the role of the immune system in cancer, while describing the methodological details that have been successfully implemented on cancer treatments and that may hold the key to improved therapeutic approaches.

Asunto(s)

Inmunoterapia , Neoplasias , Antígenos , Humanos , Masculino , Neoplasias/genética , Neoplasias/terapia