B-Cell Mediated Antimelanoma Immunity
Abstract
Fiscal Year 2016 (FY16) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas: (1) Melanoma and (2) Immunotherapy. FY16 PRCRP Military Relevance Focus Areas: Gap in cancer treatment. Melanoma is a rare type of skin cancer that causes majority of skin cancer-related death. Prolonged sunlight exposure is a major risk factor for this disease. Therefore, Veterans and other workers who have frequent exposure to sunlight during their service period come under the risk for developing melanoma. At present, immunotherapies that specifically kill cancer cells through activated CD8+ T cells (immune cells) are predominantly effective against melanoma, but more than 50% of patients do not respond to this class of drugs. Therefore, there is an unmet need to determine the factors that are associated with effectiveness of these drugs. Recently, from mouse and human studies, we found that in addition to CD8+ T cells, other immune cells called B cells also participated in melanoma growth suppression in response to TLR-7/8 agonist (3M-052) immunotherapy. The objective of this study to identify the mechanism by which immunotherapy induced B cells provide help to CD8+ T cells for melanoma growth suppression and reveal the importance of activated B cells in generation of effective CD8+ T cell immunity and clinical outcomes in response to anti-PD-1 antibody therapy (Food and Drug Administration [FDA]-approved immunotherapy). Our study will pave the way to discover new therapeutic interventions through understanding the role of B cells in developing anti-melanoma immunity. Therefore, this study may discover better treatment options for melanoma and/or metastatic melanoma patients. It will help to determine whether immunotherapy induced B cells are important for making FDA-approved anti-PD-1 therapy more effective for patients and may also reveal B cell-associated biomarkers of response to anti-PD-1 antibody therapy. Evaluating the role of activated B cells in generating/enhancing anti-melanoma immunity through this study will help to design future clinical trials based on activating B cell and CD8+ T cells combination therapy. We can further take these findings directly from bench to bedside through clinically available TLR-7/8 agonist and FDA-approved anti-PD1 antibody combination therapy. This study may also reveal B cell-associated biomarkers of response to anti-PD-1 antibody therapy. Melanoma is one of the most frequently diagnosed cancers among Department of Veterans Affairs (VA) cancer patients, and available therapies are less effective against this cancer. Our study will pave the way to discover new therapeutic interventions through understanding the role of B cells in developing anti-melanoma immunity. Thus, the proposed studies are highly relevant to military active duty Service members and their families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710611
Entities
People
- Manisha Singh
Organizations
- United States Army
- University of Texas at Austin