Cellular Phenotypes in Cancer Patient Spleen and Peripheral Blood

Abstract

Abstract Adoptive cellular therapy (ACT) has progressed; however, it remains ineffective for most solid tumors. Further, neoadjuvant patients frequently lack tumor tissue sufficient to isolate and expand tumor infiltrating lymphocytes (TIL’s) that are the primary source of T-cells for ACT. However, patients with tumors near the splenic vasculature often undergo a splenectomy, providing a cellular resource for ACT. We document herein that spleens provide a high frequency and number of CD8+ T-cells, with low expression of exhaustion markers (program death ligand-1 (PD-1), T-cell immunoglobulin and mucin domain containing-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3)) relative to the peripheral blood (PB). The memory phenotypes of these CD8+ T-cells (predominantly central and transitional) support their potential for expansion and their high frequency of PD-1 expression indicates tumor specificity as PD-1, is a surrogate for tumor specificity. Further, spleens have a low frequency of myeloid derived suppressor cells (MDSCs) subsets vs. patient PB. Our preliminary studies with spleens from 19 abdominal tumor patients revealed that the spleens, relative to the PB from the same patients, have a significantly higher frequency of CD8+ and PD-1+CD8+ T-cells, including central and transitional memory T-cells. Further, the CD8+PD-1+ T-cells in the spleen also have a low expression of TIM-3 and LAG-3 suggesting minimal exhaustion as supported by ELISPOT analysis of tumor specific CD8+ T-cells responses. Based on our studies we suggest that resected spleens from cancer patients including pancreatic ductal adenocarcinoma (PDAC) patients can provide a valuable source for ACT due to their high frequency of CD8+PD-1+ T-cells.