Abstract

Abstract Traditional assessments of T cells killing cancer cells are routinely done in two-dimensional cell culture wells and plates. The general methods comprise developing a cancer cell monolayer then overlaying it with T cells, or, worse, pre-mixing cancer cells with T cells before placing the mixture into culture wells/dishes. Such methods obviously force cancer cell-T cell interactions. This is not physiological, since T cells must migrate to tumors for cancer cell killing to even occur. Migration is a little-explored, yet central parameter ignored in 2D killing assays. There is no tumor cell killing by T cells if there is no T cell migration, biased or unbiased. Our work making use of novel 3D multi-compartments organoids systems identifies key molecules regulating pathways for T cell migration in 3D. We are currently testing molecules currently FDA-approved or in clinical trials that block or enhance T cell killing of cancer cells by blocking or enhancing T cell migration through a first-of-its-kind 3D killing assay that we developed. Citation Format: Adrian Johnston, Frisco Du, Zeqi Wan, Cameron Lee, Yeongseo Lim, Michelle Bessiake, Praful Nair, Pei-Hsun Wu, Denis Wirtz. Modulating T cell tumor infiltration by modulating T cell migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3536.

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