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

Effective immunotherapy options for patients with non-small cell lung cancer (NSCLC) are becoming increasingly available. The immunotherapy focus has been on tumor-infiltrating 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 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 (IFNγ 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 NSCLC immunotherapy. .