Clarke, James, Panwar, Bharat, Madrigal, Ariel, Singh, Divya, Gujar, Ravindra, Wood, Oliver, Chee, Serena, Jamie Tzu Wen, Eschweiler, Simon, King, Emma, Awad, Amiera, Hanley, Christopher, Mccann, Katy, Bhattacharyya, Sourya, Woo, Edwin, Alzetani, Aiman, Seumois, Gregory, Thomas, Gareth, Ganesan, Anusha-Preethi, Friedmann, Peter, Sanchez-Elsner, Tilman, Ay, Ferhat, Ottensmeier, Christian and Vijayanand, Pandurangan (2019) Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer. The Journal of Experimental Medicine, 216 (9), 2128-2149. (doi:10.1084/jem.20190249).
Abstract
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.
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