Abstract 5130: Immune profiling of malignant effusion from metastatic gastric cancer patients as a predictive biomarker for immune checkpoint inhibitors
Authors: Kwon Woo Sun , Lim So Jung , Lee Won Suk , Jo Eunji , Kim Hyun-jeong , Lee Kyung Hee , Chung Hyun Cheol , Rha Sun Young 
Published: July 2016

Many types of cancers are able to circumvent immune surveillance by the host's immune system. It has been well established that many tumor infiltrating T cells are in a state of non-responsiveness due to the immune suppressive tumor microenvironment. The main mechanisms of T cells that confer suppressive anti-tumor immune response in tumor microenvironment could be regulatory T cells (Treg) and exhausted T cells. In advanced stage cancer patients, detailed evaluation of Treg cells in tumor microenvironment is hampered by limitation for enough tumor tissue, because surgical resection for sample is not standard treatment in these patients. In order to overcome this limitation of research, we performed the studies using lymphocytes and tumor cells isolated from malignant effusion including pleural effusion or ascites from advanced gastric cancer patients.

We collected 25 malignant effusion specimens from advanced gastric cancer patients, including 20 paired peripheral blood samples. Lymphocytes from malignant effusions and peripheral bloods were analyzed for subtype of Memory, Activated T cell and Treg cells, and expressions of inhibitory molecule using by flow cytometry. To evaluate the expression of PD-L1, we used the tumor cells of malignant effusions.

Firstly, the percentage of CD8+ T cells in malignant effusion seems to increase compared to those in peripheral blood, but the percentage of CD4+ T in malignant effusion were significantly lower than those in peripheral blood. Interestingly, the percentage of CD45RO+ (Memory) on CD4+ and CD8+ T cells was significantly higher in malignant effusion than peripheral blood. And Early activated molecule (CD69 and CD25) on CD4+ and CD8+ T cells was significantly higher in malignant effusion than peripheral blood. The percentage of PD-1 expression on CD8+ T cells was significantly higher in malignant effusion than peripheral blood (p = 0.017). And the percentage and MFI of Treg cells (Foxp3+/CD4 T cell) tend to increase in malignant effusion was comparable with those of peripheral blood but did not show the statistical significance. Collectively, we found that T cells derived from malignant effusion demonstrated the exhausted phenotype showing highly expression of PD-1, compared to those from peripheral blood. Finally, the PD-L1 expression on tumor cells from malignant effusions was 0.04∼12.78%. The upregulation of PD-1 on Treg cells and PD-L1 on tumor cell of malignant effusions could be a potential predictive marker and therapeutic target for immune checkpoint blockade.

Citation Format: Woo Sun Kwon, So Jung Lim, Won Suk Lee, Eunji Jo, Hyun-jeong Kim, Kyung Hee Lee, Hyun Cheol Chung, Sun Young Rha. Immune profiling of malignant effusion from metastatic gastric cancer patients as a predictive biomarker for immune checkpoint inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5130.