CD8 T cells infiltrating tumors are largely dysfunctional, but whether a subset maintains superior functionality remains ill defined. By high-dimensional single cell analysis of millions of CD8 T cells from 53 individuals with lung cancer, we defined those subsets that are enriched in tumors compared with cancer-free tissues and blood. Besides exhausted and activated cells, we identified CXCR5 TIM-3 CD8 T cells with a partial exhausted phenotype, while retaining gene networks responsible for stem-like plasticity and cytotoxicity, as revealed by single cell sequencing of the whole transcriptome. Ex vivo, CXCR5 TIM-3 CD8 T cells displayed enhanced self-renewal and multipotency compared with more differentiated subsets and were largely polyfunctional. Analysis of inhibitory and costimulatory receptors revealed PD-1, TIGIT, and CD27 as possible targets of immunotherapy. We thus demonstrate a hierarchy of differentiation in the context of T cell exhaustion in human cancer similar to that of chronically infected mice, which is further shown to disappear with disease progression.

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Background: Robotic surgery is increasingly used to resect lung cancer. However costs are high. We compared costs and outcomes for robotic surgery, video-assisted thoracic surgery (VATS), and open surgery, to treat non-small cell lung cancer (NSCLC). Significantly more lymph node stations were removed (P<0.001), and median length of stay was shorter (4, 5 and 6 days, respectively; P<0.001) in the robotic than VATS and open groups. Estimated costs were 82%, 68% and 69%, respectively, of the regional health service reimbursement for robotic, VATS and open approaches. Discussion: Robotic surgery for early lung cancer was associated with shorter stay and more extensive lymph node dissection than VATS and open surgery. Duration of surgery was shorter for robotic than VATS. Although the cost of robotic thoracic surgery is high, the hospital makes a profit.

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