Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer

High numbers of tissue-resident memory T (TRM) cells are associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors are poorly understood. Here, single-cell and bulk transcriptomic analysis of TRM and non-TRM cells present in tumor and normal lung tissue from patients with lung cancer revealed that PD-1–expressing TRM cells in tumors were clonally expanded and enriched for transcripts linked to cell proliferation and cytotoxicity when compared with PD-1–expressing non-TRM cells. This feature was more prominent in the TRM cell subset coexpressing PD-1 and TIM-3, and it was validated by functional assays ex vivo and also reflected in their chromatin accessibility profile. This PD-1+TIM-3+ TRM cell subset was enriched in responders to PD-1 inhibitors and in tumors with a greater magnitude of CTL responses. These data highlight that not all CTLs expressing PD-1 are dysfunctional; on the contrary, TRM cells with PD-1 expression were enriched for features suggestive of superior functionality.

Source: The Journal of Experimental Medicine - September 1, 2019 Category: Internal Medicine Authors: Clarke, J., Panwar, B., Madrigal, A., Singh, D., Gujar, R., Wood, O., Chee, S. J., Eschweiler, S., King, E. V., Awad, A. S., Hanley, C. J., McCann, K. J., Bhattacharyya, S., Woo, E., Alzetani, A., Seumois, G., Thomas, G. J., Ganesan, A.-P., Friedmann, P. Tags: Solid Tumors, Tumor Immunology Articles Source Type: research