University of Virginia, USA
Posters-Accepted Abstracts: J Cancer Sci Ther
Immunotherapy has recently emerged as a promising modality in cancer treatment leading to the approval of immune checkpoint inhibitors in few malignancies including melanoma and lung cancer. Tumor-infiltrating lymphocytes (TILs) play a major role in anti-tumor immune responses and their presence is correlated with survival in a variety of tumors. However, these TILs do not reach the pancreatic cancer (PC) cells in significant numbers due to the presence of stroma and suppressive microenvironment. In addition, some colorectal cancers (CRC) have low immune score, a score that was recently described by Galon et al to assess the presence of TILs in CRC. Furthermore, one of the leading causes for immune suppression is elevated expression of PD-L1 either by the tumor cells or the surrounding regulatory cells, resulting in dysfunction of TILs. There is recent evidence to suggest that chemo-radiation therapy (CRT) can increase the presence of TILs in the PC and CRC microenvironment, leading to production of interferon-├?┬│ (IFN-├?┬│), which could increase the expression of PD-L1 through a negative feedback loop. We are currently investigating the combination of anti- PD-1 inhibitor and CRT in patients with pancreatic cancer and rectal cancer. Testing this combined modality in the neo-adjuvant setting will allow us to study the safety of this approach and its effect on the tumor microenvironment by comparing TILs and other effector (NK, macrophages) and suppressor immune cells (T-regs, MDSCs) and receptors (PD-L1, CTLA-4) pre- and post- treatment. Finally, we will study the correlation between these immune biomarkers and clinical outcomes.
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