[Inflammageing in patients with idiopathic pulmonary fibrosis (IPF)]. / Inflammageing en pacientes con fibrosis pulmonar idiopática (FPI).

METHODS: We took Peripheral blood samples from adult patients over 60 years of age with a confirmed diagnosis of IPF through biopsy or clinical criteria. Plasma separation was performed, and proinflammatory cytokines were measured using CBA. This study received approval from the ethics and research committee of the Colombian Pulmonological Foundation. RESULTS: Patients with IPF exhibited an increase in cytokines such as IL-4, INFy, and IL-6 compared to healthy older adults. CONCLUSION: Inflammatory disease has been associated with the development and coexistence of multiple chronic non-communicable diseases that have a higher incidence after 65 years of age. The involvement of adaptive immunity in the pathogenesis of IPF has been described as an imbalance in the Th1/Th2 lymphocyte response. Further studies are required to identify additional markers of immunosenescence that correlate with IPF.

OBJETIVO: Identificar citoquinas proinflamatorias en el plasma de pacientes con FPI residentes en la altura de Bogotá. MÉTODOS: Se tomaron muestras de sangre periférica de pacientes adultos mayores de 60 años, con diagnóstico de FPI confirmado por biopsia o por criterios clínicos. Se realizó la separación de plasma y se midieron citoquinas proinflamatorias por CBA. Este trabajo fue aprobado por el Comité de Ética e Investigaciones de la Fundación Neumológica Colombiana. RESULTADOS: Los pacientes con FPI mostraron un aumento de citocinas como la IL-4, INFy e IL-6, en comparación con adultos mayores sanos. CONCLUSIÓN: El inflammaging ha sido asociado con el desarrollo y coexistencia de múltiples enfermedades crónicas no transmisibles que tienen mayor incidencia después de los 65 años. Se ha descrito la participación de la inmunidad adaptativa con la patogénesis de la FPI, como un desbalance en la respuesta de linfocitos Th1/Th2. Es necesario realizar más estudios que permitan identificar otros marcadores de inmunosenescencia que se correlacionen con la FPI.

Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: Systematic review and meta-analysis.

The tumor immune infiltrate has an impact on cancer control and progression, additionally a growing body of evidence has proposed the role of neoadjuvant chemotherapy in modulating the contexture of the tumor immune infiltrate. Here, we performed a systematic review to evaluate the effect of chemotherapy in the immune infiltration of breast cancer tumors. We systematically searched Pubmed/MEDLINE, EMBASE, CENTRAL, and BVS databases with a cutoff date of 11/06/2022. Studies in patients with pathological diagnosis of BC, whose first line of treatment was only NAC, were included. Only published experimental studies that measured tumor immune infiltrate before and after NAC by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHQ), or transcriptome were included. Reviews, studies with animal models and in-vitro models were excluded. Studies in which BC was not the primary tumor or studies with patients who received other types of neoadjuvant therapy were also excluded. The NIH quality assessment tool for before and after studies without control was used. We included 32 articles that evaluated the proximal tumor microenvironment before and after neoadjuvant chemotherapy in 2072 patients who received NAC as first line of treatment and who were evaluated for immune infiltrate in the pre- and post-chemotherapy tumor sample. Results were divided into two major categories immune cells and in-situ expression of immune checkpoints and cytokines. Qualitative synthesis was performed with the 32 articles included, and in nine of them a quantitative analysis was achieved, resulting in six meta-analyses. Despite high heterogeneity among the articles regarding treatment received, type of tumor reported, and techniques used to evaluate immune infiltrate, we found a significant decrease of TILs and FoxP3 expression after neoadjuvant chemotherapy. The study protocol was registered in PROSPERO 2021 (Protocol ID: CRD42021243784) on 6/29/2021.

Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients.

Breast cancer is the leading cause of cancer deaths in women worldwide. It has been observed that the incidence of breast cancer increases linearly with age after 45, which suggest a link between cancer, aging, and senescence. A growing body of evidence indicates that the immunosuppressive tumor network in breast cancer patients can lead to T-cell exhaustion and senescence. Cytotoxic chemotherapy is a common treatment for many cancers, and it is hypothesized that its efficacy may be related to immune activation. However, the effects of neoadjuvant chemotherapy on T-cell dysfunction in breast cancer patients are not fully understood. This study aimed to evaluate the impact of neoadjuvant chemotherapy on the expression of exhaustion and senescence markers in T cells in women with breast cancer. Our results showed that T cells from breast cancer patients have a reduced ability to respond to stimulation in-vitro and an increased expression of senescence and exhaustion-associated markers, such as TIM-3, LAG3, and CD57. Furthermore, we found that neoadjuvant chemotherapy has an immunomodulatory effect and reduces the expression of exhaustion markers. Our observations of the immune phenotype of T cells during neoadjuvant chemotherapy treatment highlight its ability to stimulate the immune system against cancer. Therefore, monitoring the response of T cells during chemotherapy may enable early prediction of clinical response.

Young but not older adults exhibit an expansion of CD45RA+CCR7+CD95+ T follicular helper cells in response to tetanus vaccine.

A subset of CD4+ T cells, known as T follicular helper (Tfh), provides co-stimulating signals required to establish long-term humoral immunity. Recent studies have shown a reduced frequency and functionality of this population in older adults in comparison to young adults, in response to vaccination. To evaluate whether memory generation of circulating Tfh (cTfh) cells contributes to this phenomenon, the memory subpopulations of cTfh, and their activation degree, were evaluated both ex-vivo and in-vitro, in response to the model antigen tetanus toxoid (TT) after the first dose of tetanus vaccine. Here, we report a lower frequency of cTfh after vaccination in older adults compared to young adults. Moreover, whereas cTfh from older adults preferably expanded with an effector memory phenotype, young adults experienced a temporal increase of CCR7+CD45RA+ cTfh cells, which also displayed higher levels of CD95, CD40L, CXCR3, and Bcl-6 upon antigen re-encounter. This phenotype was confirmed using automatized algorithm. In conclusion, our results suggest that an age-related loss of heterogeneity and an expansion of more differentiated memory cells within the cTfh compartment could affect the responsiveness of older individuals to vaccines, making this phenotype a characteristic feature of immunosenescence.

Personalized neoantigen-based cancer immunotherapy. A literature review / Inmunoterapia personalizada contra el cáncer basada en neoantígenos. Revisión de la literatura

Abstract Introduction: The progress made in cancer immunotherapy and the clinical response of patients who have undergone this type of therapy have made it the fourth pillar of cancer treatment. Objective: To briefly describe the biological rationale of personalized neoantigen-based cancer immunotherapy, the current perspectives regarding its development, and some of the clinical outcomes achieved with this therapy. Materials and methods: A literature search was performed in PubMed, Scopus and EBSCO using the following search strategy: type of articles: original experimental studies, clinical trials, and narrative and systematic reviews addressing methods to identify mutations found in tumors and cancer immunotherapy strategies based on neoantigen-based vaccines; study population: humans and animal models; publication period: January 1989 - December 2019; language: English and Spanish; search terms: "Immunotherapy", "Neoplasms", "Mutation" and "Cancer Vaccines". Results: The initial search started with 1 344 records. Once duplicates were removed (n=176), 780 studies were excluded after reading their abstract and title. The full text of 338 articles was read to confirm which met the inclusion criteria, finally including 73 studies for full analysis. All articles retrieved were published in English and were mainly conducted in the USA (43.83%) and Germany (23.65%). In the case of original studies (n=43), 20 were performed in humans only, 9 in animals only, 2 in both models, and 12 used in silico methodology. Conclusion: Personalized cancer immunotherapy with tumor neoantigen-based vaccines is strongly emerging as a new alternative to treat cancer. However, to achieve its appropriate implementation, it is necessary to use it in combination with conventional treatments, produce more knowledge that helps clarify cancer immunobiology, and reduce the costs associated with its production.

Resumen Introducción. Los avances que se han hecho en inmunoterapia contra el cáncer y la respuesta clínica de los pacientes que han recibido este tipo de terapia la han convertido en el cuarto pilar para el tratamiento del cáncer. Objetivo. Describir brevemente el fundamento biológico de la inmunoterapia personalizada contra el cáncer basada en neoantígenos, las perspectivas actuales de su desarrollo y algunos resultados clínicos de esta terapia. Materiales y métodos. Se realizó una búsqueda de la literatura en PubMed, Scopus y EBSCO utilizando la siguiente estrategia de búsqueda: tipo de artículos: estudios experimentales originales, ensayos clínicos y revisiones narrativas y sistemáticas sobre métodos de identificación de mutaciones generadas en los tumores y estrategias de inmunoterapia del cáncer con vacunas basadas en neoantígenos; población de estudio: humanos y modelos animales; periodo de publicación: enero de 1989 a julio de 2019; idioma: inglés y español; términos de búsqueda: "Immunotherapy", "Neoplasms", "Mutation" y "Cancer Vaccines". Resultados. La búsqueda inicial arrojó 1 344 registros; luego de remover duplicados (n = 176), 780 fueron excluidos después de leer su resumen y título, y se evaluó el texto completo de 338 para verificar cuáles cumplían con los criterios de inclusión, seleccionándose finalmente 73 estudios para análisis completo. Todos los artículos recuperados se publicaron en inglés, y fueron realizados principalmente en EE. A (43.83%) y Alemania (23.65%). En el caso de los estudios originales (n=43), 20 se realizaron únicamente en humanos, 9 solo en animales, 2 en ambos modelos, y 12 usaron metodología in silico. Conclusión. La inmunoterapia personalizada contra el cáncer con vacunas basadas en neoantígenos tumorales se está convirtiendo de forma contundente en una nueva alternativa para tratar el cáncer. Sin embargo, para lograr su implementación adecuada, es necesario usarla en combinación con tratamientos convencionales, generar más conocimiento que contribuya a aclarar la inmunobiología del cáncer y reducir los costos asociados con su producción.

Human immune response to SARS-CoV-2: What is known? A scoping review / Respuesta inmune humana al SARS-CoV-2: ¿Qué se conoce? Una scoping review

Monitoring literature on the broad spectrum of the human immune response to SARS-CoV-2 is important to understand the mechanisms and progression of COVID-19. The present study undertakes a scoping review of the literature on human immune response to SARS-CoV-2 to determine the characteristics of innate and adaptive responses, as well as biomarkers and cells that play a role in the development of the infection. We searched papers in MEDLINE/PUBMED and EMBASE databases published since December 1st 2019 to to April 9th 2020 from which we selected 56 for this study. We found that the immune response is characterized by high levels of acute phase reactants, neutrophilia, low levels of NKs and eosinophils, lymphopenia, cytokine storm syndrome, exhausted T cells, impaired cytotoxic response, inadequate helper response and production of specific antibodies; concluding that immune dysregulation correlates with disease severity and high mortality.

El seguimiento de la literatura sobre la respuesta inmune humana al SARS-CoV-2 es importante para comprender los mecanismos y la progresión de COVID-19. En el presente estudio se realizó un Scoping Review de la literatura sobre la respuesta inmune humana al SARS-CoV-2 para determinar las características de la respuesta inmune innata y adaptativa, así como biomarcadores y células que juegan un papel en el desarrollo de la infección. Buscamos artículos en las bases de datos MEDLINE / PUBMED y EMBASE publicados desde el 1 de diciembre de 2019 hasta el 9 de abril de 2020, de los cuales seleccionamos 56 publicaciones para este estudio. Encontramos que la respuesta inmune se caracteriza por altos niveles de reactantes de fase aguda, neutrofilia, bajos niveles de NKs y eosinófilos, linfopenia, síndrome de tormenta de citoquinas, linfocitos T agotados, respuesta citotóxica alterada, respuesta T helper inadecuada y producción de anticuerpos específicos. En conclusión, el desequilibrio inmune se correlaciona con la severidad y la mortalidad de la enfermedad.

Immunosenescence Study of T Cells: A Systematic Review.

Background: Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders. This decline in immune function is termed as immunosenescence; however, the mechanisms are not fully elucidated. Experimental approaches of adaptive immunity, particularly for T cells, have been the main focus of immunosenescence research. This systematic review evaluates and discusses T cell markers implicated in immunosenescence. Objective: To determine the best flow cytometry markers of circulating T cells associated with immunosenescence. Methods: We systematically queried PubMed, MEDLINE, EBSCO, and BVS databases for original articles focused on two age groups of healthy humans: 18-44 (young adults) and >60 (older adults) years. In accordance with the Cochrane methodology, we synthesized data through qualitative descriptions and quantitative random effects meta-analysis due to extensive heterogeneity. Results: A total of 36 studies conducted in the last 20 years were included for the qualitative analysis and four out of these studies were used to perform the meta-analysis. A significant decrease in naïve T cell subset was observed in older adults compared to young adults. Primary markers used to identify senescent cells were loss of CD28 and increased expression of CD57 and KLRG1 in terminally-differentiated memory T cell subset in older adults. Moreover, we observed an increase in proinflammatory cytokines and decrease in telomere length in old adult T cells. It was not possible to perform quantitative synthesis on cell markers, cytokines, and telomere length because of the significant variations between the groups, which is attributed to differences in protocols and unreported measurements, thus generating a high risk of bias. Conclusions: Heterogeneity among studies in terms of data report, measurement techniques and high risk of bias were major impediments for performing a robust statistical analysis that could aid the identification of eligible flow cytometry markers of immunosenescence phenotype in T cells.

Virulence and immune response induced by Mycobacterium avium complex strains in a model of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice.

The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.