Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non-Small Cell Lung Cancer Patients

Effective immunotherapy options for patients with nonsmall cell lung cancer (NSCLC) are becoming increasingly available. The immunotherapy focus has been on tumorinfiltrating T cells (TILs); however, tumor-infiltrating B cells (TIL-Bs) have also been reported to correlate with NSCLC patient survival. The function of TIL-Bs in human cancer has been understudied, with little focus on their role as antigen-presenting cells and their influence on CD4(+) TILs. Compared with other immune subsets detected in freshly isolated primary tumors from NSCLC patients, we observed increased numbers of intratumoral B cells relative to B cells from tumor-adjacent tissues. Furthermore, we demonstrated that TIL-Bs can efficiently present antigen to CD4(+) TILs and alter the CD4(+) TIL phenotype using an in vitro antigen-presentation assay. Specifically, we identified three CD4(+) TIL responses to TIL-Bs, which we categorized as activated, antigen-associated, and nonresponsive. Within the activated and antigen-associated CD4(+) TIL population, activated TIL-Bs (CD19(+)CD20(+)CD69(+)CD27(+)CD21(+)) were associated with an effector T-cell response (IFN gamma(+) CD4(+) TILs). Alternatively, exhausted TIL-Bs (CD19(+)CD20(+)CD69(+)CD27-CD21-) were associated with a regulatory T-cell phenotype (FoxP3(+) CD4(+) TILs). Our results demonstrate a new role for TIL-Bs in NSCLC tumors in their interplay with CD4(+) TILs in the tumor microenvironment, establishing them as a potential therapeutic target in NSCLCimmunotherapy. (C) 2017 AACR.