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Objective: Mouse lung cancer cell lines 393P and 344SQ are derived from KrasLA1/+ p53R172HΔG mice and have different metastatic potential in immunocompetent mice. 393P cells have local primary tumor growth but do not form metastatic lesions while344SQ cells form a primary tumor and metastatic lesions when injected into the subcutaneous space of 129 sv mice. We postulated that the presence of lymphocytes led to differential phenotype for these two cells. In order to test this hypothesis, we used novel cellular 4D ex vivo lung cancer metastasis model created using rat lung where we can determine the impact of lymphocytes on number of circulating tumor cells and formation of metastatic lesions. Methods: We grew GFP tagged 393p or 344SQ mice cells on cellular 4D lung model as control group and for treatment group we added activated lymphocytes on day 0, day 3 and day 5. These activated lymphocytes were obtained by harvesting spleen from mice injected with 393p and 344SQ (1Million) in 129Sv mice. Cellular model with GFP tagged CTCs were counted on day 6 and day 11 by Flow sorting instrument. Primary tumor was removed on day 7 and metastatic lesions were allowed to grow till day 14. Tissues were processed for HE p=0.02) while no effect was found on CTCs from 344SQ growing models (13841 vs 7072; p=0.27). Furthermore, there were significantly less metastatic lesions formed with 393p growing cellular model in the presence of lymphocytes (p=0.008), while there was no impact of lymphocytes on formation of metastatic lesion with 344SQ. Conclusion: Lymphocytes inhibit metastatic lesion formation in 393P cell lines but not 344SQ cell lines in cellular lung model. The cellular 4D lung recapitulates the phenomenon exhibited by in vivo in presence of activated lymphocytes. The model can be used to study the role of different components of a tumor’s microenvironment in tumor metastasis. Citation Format: Dhruva Kumar Mishra, Ross A. Miller, Min P. Kim. Lymphocytes inhibits the tumor metastasis in 4D cellular lung model by reducing the number of live CTCs in circulation [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B22.