The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided to us by the authors.
Use the dropdown menu or ‘Previous’ and ‘Next’ buttons to navigate the list.
D.S. Thommen et al., Nature Medicine volume 24, pages 994–1004 (2018)
Summary
Evidence from murine chronic infection models suggests that the expression level of PD-1 can distinguish CD8+ T cell subsets that respond differently to PD-1 blockade. To assess whether similar T cell states exist in human cancer, we isolated and characterized three subpopulations of intratumoral T lymphocytes (TILs) with high, intermediate and negative PD-1 expression from non-small cell lung cancer specimens. We identified a transcriptionally distinct CD8+ T cell subset with bright PD-1 expression that was specific to the tumor (termed PD-1T TILs). Compared to T cells with intermediate or negative PD-1 expression, PD-1T TILs were highly proliferative and contained an enriched capacity for tumor recognition. While PD-1T TILs lost canonical T cell functions, they secreted the chemoattractant CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. The presence of a high number of PD-1T TILs in pretreatment biopsies was strongly predictive for response and survival following anti-PD-1 treatment in a small cohort of NSCLC patients.
Future impacts of the findings
The observation that PD-1T TILs are a highly proliferative subset and acquire CXCL13 secretion suggests that these cells are not ‘exhausted’ in the sense of complete loss of effector function, but rather display an altered functionality at the tumor site. Their intrinsically high capacity for tumor recognition indicates a crucial role for the anti-tumor immune response and makes them an attractive target for novel T cell directed therapies. The predominant localization of PD-1T TILs within tertiary lymphoid structures suggests a potential role of these structures for immunotherapy response. Finally, the striking correlation of PD-1T TILs present in the tumor with therapy response makes them a potential novel biomarker for PD-1/PD-L1 targeting therapies.
