Abstract 532: Irradiation alters the tumor microenvironment of orthotropic pancreatic tumor in favoring the infiltration of PD1+CD8 and G-MDSC and the delivery of immune checkpoint blockade therapy agents

Abstract

Immunotherapy (IT) is trending on cancer research, but its efficacy heavily depends on the tumor microenvironment (TME). IT is also frequently combined with radiation therapy (RT). Here, we explored the effect of radiation therapy (RT) on the TME and its consequence on the combination of IT using a syngeneic orthotropic UN-KC6141 PDAC tumor model. The result of immunohistochemical staining (IHC) demonstrates that 25Gy of IR could effectively decrease the number of CD31+ vessels, but significantly increase distribution area of Dextran, an indication of vessel normalization. The normalized tumor vessels are more effectively on delivering ICBT (immune checkpoint blockade therapy) drug delivery as shown by the increase of anti-PD-L1 antibody in irradiated tumor. In addition, we also found that the number of PD1 + CD8 + Tc cells and Ly6G + G-MDSC is also increased in irradiated tumor. This indicates that RT could alter TME of pancreatic tumor in favoring the combination with IT, not only alters an immune desert tumor to become an immune infiltrating tumor, but also enhances the delivery of ICBT agents. For this tumor model, the combination of RT with anti-PD-L1 or anti-Ly6G therapy could be effective. To test this hypothesis, the combination of RT with ICBT agents was performed. The preliminary results show that anti-PD-L1 ICBT could enhance the efficacy of RT on decreasing tumor burden. The combination of anit-Ly6G therapy with RT is currently under investigation. Citation Format: Yu Hung Lee. Irradiation alters the tumor microenvironment of orthotropic pancreatic tumor in favoring the infiltration of PD1+CD8 and G-MDSC and the delivery of immune checkpoint blockade therapy agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 532.