In a mouse model of melanoma-associated vitiligo (MAV), Molodtsov and Khatwani et al. found that injected gp100-specific pmel T cells inhabited various organs, where they expressed resident memory (Trm) markers, but with tissue-specific transcriptional profiles. In naive recipients parabiosed with MAV/pmel mice, circulating memory T cell phenotypes conferred protection against lung, but not LN melanoma rechallenge, suggesting that Trm cells were required to restrict LN metastasis. Trm cells were detected in patient melanoma-infiltrated LNs, and a LN-Trm signature indicated better prognosis in patients with regional LN metastasis.
Contributed by Alex Najibi
ABSTRACT: The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8(+) T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.
Author Info: (1) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (2) Department of Microbiology and Immunology, The Geisel School
Author Info: (1) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (2) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (3) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (4) Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (5) Department of Molecular and Systems Biology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (6) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (7) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (8) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (9) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (10) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (11) Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (12) Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (13) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (14) Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (15) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. (16) Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (17) Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (18) Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (19) Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA. (20) Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (21) Department of Medicine and Mays Cancer Center, University of Texas Health, San Antonio, TX 78229, USA. (22) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. (23) Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: chao.cheng@bcm.edu. (24) Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Norris Cotton Cancer Center, The Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. Electronic address: mary.jo.turk@dartmouth.edu.
