In vitro-generated MART-1-specific CD8 T cells display a broader T-cell receptor repertoire than ex vivo naïve and tumor-infiltrating lymphocytes.

The differentiation of human hematopoietic stem cells into CD8 T cells can be achieved in vitro with the OP9-DL4 system. We considered that in the absence of medullary thymic epithelial cells, which serve to restrict the breath of the T-cell receptor (TCR) repertoire by expressing tissue-restricted antigens, a distinct repertoire would be generated in vitro. To test this notion, we compared the TCR-Vα/Vß (TRAV/TRBV) gene usage of major histocompatibility complex-restricted antigen (MART-1)-specific T cells generated in vitro to that from ex vivo naïve T cells and tumor-infiltrating lymphocytes (TILs) using high-throughput DNA sequencing. In contrast to naïve T cells and TILs, which showed the expected narrow TRAV repertoire, in vitro-generated MART-1-specific T cells used almost all TRAV gene families and displayed unique CDR3 lengths. Our work demonstrates that the OP9-DL4 system supports the creation of a broad antigen-specific TCR repertoire, suggesting that T cells generated in vitro may undergo a different set of selection events that otherwise constrains the TCR repertoire of thymus-derived T cells.

[New therapeutic advances in patients with lung cancer immunosuppressed with chronic lung diseases in the period 2014-2022 from the review of the literature.] / Nuevos avances terapéuticos en pacientes con cáncer de pulmón inmunosuprimidos con enfermedades crónicas pulmonares en el periodo 2014-2022 a partir de la revisión de la literatura.

Lung cancer is a malignant neoplasm with a high prevalence and mortality, more so in patients with respiratory comorbidities, whose cells have a massive proliferation capacity in the lung tissue, managing to invade other organs, which deteriorates the patient's physical and emotional state, decreasing their quality of life and defense system; therefore, treatment today is not sufficient for patient survival and there has been evidence of a certain evolution in the treatment of the disease or early detection to prevent it. This article aimed to analyze the new therapeutic advances in patients with lung cancer associated with chronic lung diseases in the period 2014-2022 based on a review of the literature. Several parameters were used to limit the search, extrapolating the articles of interest, validating fifty three articles, six doctoral theses and two books, which were in Spanish and English.The various search strategies used were keywords, subject and author follow-up. The sections developed in this review are the concept of Lung Cancer (LC), clinical manifestations, risk factors, relationship between LC and chronic lung diseases, diagnosis, treatment, prevention and new therapeutic advances. All the filtered information of the selected articles shows us the importance that the use of various biomarkers is taking for its early detection; however, the transfer of antitumor T cells in patients with underlying lung disease had an efficiency of 48.

El cáncer de pulmón es una neoplasia maligna de gran prevalencia y mortalidad, más en pacientes con comorbilidades respiratorias, cuyas células tienen una capacidad de proliferación masiva en el tejido pulmonar logrando invadir otros órganos, deteriorando el estado físico y emocional del paciente, su calidad de vida y sistema de defensa. Además, el tratamiento no es suficiente hoy en día para la supervivencia del paciente y se ha evidenciado cierta evolución en la terapéutica de la enfermedad o su detección precoz. El objetivo fue analizar los nuevos avances terapéuticos en pacientes con Cáncer de Pulmón asociado a enfermedades crónicas pulmonares en el periodo 2014-2022 a partir de la revisión de la literatura. Se aplicaron diversos parámetros para la limitación de búsqueda, extrapolando los artículos de interés, siendo validados cincuenta y tres artículos, seis tesis doctorales y dos libros, los cuales eran de idioma español e inglés. Las diversas estrategias de búsquedas usadas fueron las palabras claves, tema y seguimiento de autor. Los apartados desarrollados en la presente revisión fueron el concepto de cáncer de pulmón (CP), las manifestaciones clínicas, los factores de riesgo, la relación entre CP y enfermedades crónicas pulmonares, el diagnóstico, el tratamiento, la prevención y los nuevos avances terapéuticos. Toda la información filtrada de los artículos seleccionados nos pone de manifiesto la importancia que está tomando el uso de diversos biomarcadores para su detección precoz; sin embargo, la transferencia de células T antitumorales en pacientes con una enfermedad pulmonar de base presentó una eficiencia del 48%.

Regulatory T cells sense effector T-cell activation through synchronized JunB expression.

To maintain immune tolerance, effector T-cell (Teff) responses must be checked by the regulatory T cells (Tregs) in time. It remains incompletely understood how Tregs sense real-time Teff activation. Here, we report that the AP-1 transcription factor JunB, which is induced in Teffs upon T-cell receptor (TCR) activation, is also increased in Tregs by TCR stimuli. Treg-specific deletion of Junb impairs Treg identity, causes uncontrolled inflammatory cytokine production by Teffs and leads to the T-box transcription factor T-bet-dependent spontaneous inflammation. Furthermore, JunB deficiency in Tregs unleashes antitumor Teff responses in a mouse model of melanoma. We conclude that JunB alarms Tregs of the emerging Teff activation and synchronizes immune regulation with the immune reaction in autoimmunity and cancer.

Dendritic cell-based vaccine efficacy: aiming for hot spots.

Many approaches for cancer immunotherapy have targeted dendritic cells (DCs), directly or indirectly, for the induction of antitumor immune responses. DC-based vaccines have been developed using a wide variety of ex vivo DC culture conditions, antigen (Ag) source and loading strategies, maturation agents, and routes of vaccination. Adjuvants are used to activate innate immune cells at the vaccine injection site, to promote Ag transport to the draining lymph nodes (LNs) and to model adaptive immune responses. Despite years of effort, the effective induction of strong and durable antitumor T-cell responses in vaccinated patients remains a challenge. The study of vaccine interactions with other immune cells in the LNs and, more recently, in the injection site has opened new doors for understanding antitumor effector T-cell licensing and function. In this review, we will briefly discuss the relevant sites and up-to-date facts regarding possible targets for antitumor vaccine refinement. We will focus on the processes taking place at the injection site, adjuvant combinations and their role in DC-based vaccines, LN homing, and modeling vaccine-induced immune responses capable of controlling tumor growth and generating immune memory.