Analysis of defective anti-tumor responses in aged mice 4393

Description Age is one of the most important risk factors for cancer with individuals over 65 accounting for half the annual cancer burden in the United States. Many cancers that develop in the aged population are carcinomas, namely breast, colon, prostate, and lung. A characteristic shared by these adenocarcinomas is the expression of aberrantly glycosylated mucins. These mucins or tumor-associated carbohydrate antigens (TACAs) are displayed on a significant portion of breast and colorectal cancers. Thomsen-nouvelle (Tn) antigen is a TACA associated with metastasis, poor prognosis, and reduced overall survival. We sought to assess how aging impacts the anti-tumor response to a Tn-expressing colorectal tumor. We found 3-month-old mice exhibited significantly reduced tumor volume and mass compared to their 18-month-old counterparts. We found a substantial decrease in tumor-infiltrating CD4+ T, CD8+ T, and dendritic cells in aged mice. In the tumor-draining lymph node, aged mice exhibited a 4-5-fold reduction in CD4+ and CD8+ T cell numbers and a 2-fold reduction of antibody-secreting B cells. Aged T cells displayed significant functional defects including a decrease in CD8+ and CD4+ T cells producing IFNg--a key anti-tumor cytokine. Together, this work highlights significant defects in the anti-tumor response in aged mice against Tn-expressing tumors. Funding Sources Supported by NIH R01CA272724-02 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)