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. Author manuscript; available in PMC: 2022 Mar 30.
Published in final edited form as: Nat Cancer. 2021 Sep 30;2(10):1071–1085. doi: 10.1038/s43018-021-00247-z

Figure 7.

Figure 7

Immunotherapy refractory low neoantigen expressing tumors remain vulnerable to antigen-specific T cell killing. (a-d) Flow cytometric analysis of H-2Kb and PD-L1 MFI (a-b) and representative histograms of expression (c-d) following 24 hours of IFNγ stimulation (10 ng/mL) in ex vivo loSIIN tumor-derived organoids. Each organoid line was derived from a treatment refractory tumor taken from an independent animal in the indicated treatment arms in Fig. 6. Parental = un-transplanted loSIIN organoids. N = 3 no treatment, 3 αPD-1, and 2 αCD40/αPD-1 independent organoid lines. (e-f) Flow cytometric analysis of mScarletSIIN (e) and EGFP (f) expression in ex vivo tumor-derived organoids. N = same as above. (g) Images of co-cultures with ex vivo tumor-derived organoids and activated OT-1s at an effector-to-target ratio of 5:1 at day 4. (h) Schematic representation of the role of neoantigen expression level in immune evasion and response to therapeutic priming.