Prokhnevska et al. showed that tumor-DLNs from patients undergoing surgery for prostate or kidney cancer had a population of activated PD1+TCF1hi CD127hiCD28hi CD8+ T cells, which lacked effector molecules and shared TCR clonality and functional, transcriptional, and epigenetic traits with stem-like CD8+ T cells in the matched tumor. In mouse tumor models, tumor-DLN CD8+ T cells with a parallel phenotype became stem-like on initial antigen activation and then migrated to tumors. In tumors, costimulation by cDC2s and mo-DCs was required, and IFN-I and IL-12 contributed to Tcf1+ stem-like cell differentiation/acquisition of effector functions.
Contributed by Paula Hochman
ABSTRACT: Improvements in tumor immunotherapies depend on better understanding of the anti-tumor T cell response. By studying human tumor-draining lymph nodes (TDLNs), we found that activated CD8(+) T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1(+) stem-like cells in the tumor. The phenotype and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8(+) T cells. Murine tumor models revealed that tumor-specific CD8(+) T cells were activated in TDLNs but lacked an effector phenotype. These stem-like cells migrated into the tumor, where additional co-stimulation from antigen-presenting cells drove effector differentiation. This model of CD8(+) T cell activation in response to cancer is different from that of canonical CD8(+) T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8(+) T cell activation: initial activation in TDLNs and subsequent effector program acquisition within the tumor after additional co-stimulation.
Author Info: (1) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (2) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (3) Department o
Author Info: (1) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (2) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (3) Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. (4) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (5) Winship Cancer Institute of Emory University, Atlanta, GA, USA; Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA. (6) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA. (7) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (8) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (9) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (10) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. (11) Winship Cancer Institute of Emory University, Atlanta, GA, USA; Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA. (12) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA. (13) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA. (14) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA. (15) Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. (16) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA. (17) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA. (18) Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute of Emory University, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: haydn.kissick@emory.edu.
