Antigen-presenting tumor B cells impact the phenotype of CD4 tumor infiltrating T cells in lung cancer patients
Tullia C. Bruno1*, Peggy J. Ebner1, Brandon L. Moore1, Olivia G. Squalls1, Katherine A. Waugh1, Evgeniy B. Eruslanov2, Sunil Singhal2, John D. Mitchell3, Wilbur A. Franklin4, Daniel T. Merrick4, Martin D. McCarter3, Brent E. Palmer5, Jeffrey A. Kern6, Jill E. Slansky1
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO; 2Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA; 3Department of Surgery, University of Colorado School of Medicine, Aurora, CO; 4Department of Pathology, University of Colorado School of Medicine, Aurora, CO; 5Division of Allergy and Clinical Immunology, University of Colorado School of Medicine, Aurora, CO; 6Division of Oncology, National Jewish Health, Denver, CO
The focus of immunotherapy has been on CD8 and CD4 tumor infiltrating lymphocytes (TILs), however, tumor infiltrating B cells (TIL-Bs) have been understudied with no focus on their role as antigen presenting cells. We hypothesize that TIL-Bs help generate potent, long-term immune responses against cancer by presenting tumor antigens to CD4 TILs. We observed three types of CD4 TIL responses when TIL-Bs presented autologous tumor antigens. There were activated responder CD4 TILs that proliferated when combined with TIL-Bs alone, which indicates stimulation with endogenous tumor antigens. There were antigen-associated responders that required exogenous autologous tumor lysate to elicit a CD4 TIL response, and there were CD4 TILs that did not respond to antigen presentation. Within the responders, if the TIL-Bs were activated (CD27+CD21+), the CD4 TILs were Th1 CD4 T cells and if the TIL-Bs were exhausted (CD27-CD21-), the CD4 TILs were T regulatory cells. These data suggest that TIL-Bs influence CD4 TILs in NSCLC patient tumors. In conclusion, determining if TIL-Bs are activated or exhausted in NSCLC patients will determine the extent of their anti-tumor function in human cancer. Ultimately, results from this study will dictate how to target TIL-Bs in future immunotherapies.
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