Description

Antigen-presenting tumor B cells impact the phenotype of CD4 tumor infiltrating T cells in lung cancer patients

Tullia C. Bruno^1*, 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

*Corresponding author

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.