Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non–Small Cell Lung Cancer Patients
-
- Tullia C. Bruno
- 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Peggy J. Ebner
- 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Brandon L. Moore
- 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Olivia G. Squalls
- 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Katherine A. Waugh
- 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Evgeniy B. Eruslanov
- 2Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
-
- Sunil Singhal
- 2Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
-
- John D. Mitchell
- 3Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado.
-
- Wilbur A. Franklin
- 4Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Daniel T. Merrick
- 4Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Martin D. McCarter
- 3Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado.
-
- Brent E. Palmer
- 5Division of Allergy and Clinical Immunology, University of Colorado School of Medicine, Aurora, Colorado.
-
- Jeffrey A. Kern
- 6Division of Oncology, National Jewish Health, Denver, Colorado.
-
- Jill E. Slansky
- 1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
説明
<jats:title>Abstract</jats:title> <jats:p>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 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 (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. Cancer Immunol Res; 5(10); 898–907. ©2017 AACR.</jats:p>
収録刊行物
-
- Cancer Immunology Research
-
Cancer Immunology Research 5 (10), 898-907, 2017-10-01
American Association for Cancer Research (AACR)