Gavil et al. used parabiosis to characterize the migrational properties of CD8+ T cells in normal murine mammary fat pads (MFP) and orthotopic breast tumors. Conventional TRM markers derived from virus-specific memory CD8+ T cells, such as CD69 and CD103, identified MFP TRM, but failed to correlate with tumor residence. In the tumor context, CD62L, a marker typically associated with circulating non-resident T cells, was also expressed in TRM. Chronic antigen stimulation and the tumor environment drove distinct programs of residence in tumors, whereby tumor-specific stem progenitor CD8+ T cells migrate to tumors and acquire markers of exhaustion while becoming resident.
Contributed by Shishir Pant
ABSTRACT: Analyses of healthy tissue reveal signatures that identify resident memory CD8(+) T cells (T(RM)), which survey tissues without recirculating. The density of T(RM) phenotype cells within solid tumors correlates favorably with prognosis, suggesting that intratumoral residents control cancer. However, residence has not been directly tested, and intratumoral T(RM) phenotype cells could instead reflect aspects of the microenvironment that correlate with prognosis. Using a breast cancer model in mice, we found that conventional T(RM) markers do not inform the tumor residence of either bystander or tumor-specific cells, which exhibit further distinct phenotypes in the tumor microenvironment and healthy mammary tissue. Rather, tumor-specific, stem progenitor CD8(+) T cells migrate to tumors and become resident while acquiring select markers of exhaustion. These data indicate that tonic antigen stimulation and the tumor environment drive distinct programs of residence compared with healthy tissues and that tumor immunity is sustained by continued migration of tumor-specific stem cells.
Author Info: (1) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Mi
Author Info: (1) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (2) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (3) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (4) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (5) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (6) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (7) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (8) Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. (9) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. (10) Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
