A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8+ T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA−CD27− effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer

Temperamento em bubalinos: testes de mensuração Temperament in buffalos: mensurament tests

O objetivo neste trabalho foi avaliar a aplicabilidade, para búfalos (Bubalus bubalis), de testes de avaliação de temperamento, utilizados para bovinos. Foram avaliados os testes de docilidade, teste de reação a objetos novos, de tronco e de isolamento social em 12 bezerros e suas 12 mães, separadamente. Tanto os bezerros como suas mães responderam a todos os testes com vários comportamentos. Para os bezerros e as mães, os testes que promoveram maior número de comportamentos foram o de tronco e de reação a objetos novos. Houve diferenças individuais (coeficiente de variação de 32-51%) nos resultados de todos os testes tanto nos bezerros como nas mães. Os resultados individuais, em testes de isolamento social e de reação a objetos novos apresentaram correlação positiva tanto com as mães (rs = 0,76, P< 0,01) quanto com os bezerros (rs = 0,66, P< 0,01). Baseados em sensibilidade, relevância e aplicabilidade, o teste de isolamento social e o teste de tronco podem ser sugeridos para avaliarem o temperamento de bubalinos.<br>The objective of this study was to assess the applicability of temperament tests commonly used in bovines for water buffaloes (Bubalus bubalis). The tests for docility, reaction to a novel object, squeeze cage and social isolation were applied individually with 12 calves and their 12 mothers. Both calves and their mothers responded to all tests with a variety of behaviors. The tests that elicited the larger number of behaviors were the squeeze cage and the novel object. There were large individual differences (coefficients of variation of 32-51%) in the scores for all tests for calves and adults. The individual scores for the tests of isolation and novel object were significantly correlated for calves (rs = 0.66, P< 0.01) and adults (rs = 0.76, P< 0.01). Using the criteria of sensitivity (range of individual differences), responsiveness and applicability, the squeeze cage test and the isolation test seem well suited for water buffaloes

Body composition and lung cancer-associated cachexia in TRACERx

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial–mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC