Tumor infiltrating B cells (TIL-Bs) correlate with survival in patients with NSCLC, and Bruno et al. found that TIL-Bs efficiently present antigen to CD4+ T cells. “Activated” TIL-Bs led to activated (nonspecific) or antigen-associated effector CD4+ T cell responses, while “exhausted” B cells led to a non-responsive CD4+ Treg phenotype. Although the patient numbers were small, activated and exhausted TIL-B populations correlated with patient outcomes.

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 to 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 non-responsive. 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 (IFNgamma+ 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.

Author Info: (1) Immunology and Microbiology, University of Colorado School of Medicine. (2) Immunology and Microbiology, University of Colorado School of Medicine. (3) Immunology and Microbiol

Author Info: (1) Immunology and Microbiology, University of Colorado School of Medicine. (2) Immunology and Microbiology, University of Colorado School of Medicine. (3) Immunology and Microbiology, University of Colorado School of Medicine. (4) Immunology and Microbiology, University of Colorado School of Medicine. (5) Immunology and Microbiology, University of Colorado School of Medicine. (6) Division of Thoracic Surgery, University of Pennsylvania. (7) Division of Thoracic Surgery, University of Pennsylvania. (8) Surgery, University of Colorado School of Medicine. (9) Pathology, University of Colorado School of Medicine. (10) Pathology, University of Colorado School of Medicine. (11) Surgery, University of Colorado School of Medicine. (12) Division of Allergy and Clinical Immunology, University of Colorado School of Medicine. (13) Division of Oncology, National Jewish Health. (14) Immunology and Microbiology, University of Colorado School of Medicine Jill.Slansky@ucdenver.edu.