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. 2023 Jun 28;11(6):e006890. doi: 10.1136/jitc-2023-006890

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© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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PRMT5 inhibitors potentiated the therapeutic efficacy of immunotherapy. (A) PRMT5 overexpression prevents the cytotoxic effect of IFN-γ, RSL3 and erastin on murine 4T1 mammary carcinoma cells. (B) Representative blots showing the expression of NRF2, HMOX1, and KEAP1 in 4T1 cells treated with RSL3 (3 µM), erastin (8 µM) or IFN-γ (20 ng/mL) in combination with or without PRMT5 inhibitors. (C) Schematic showing the animal anti-PD1 administration scheme. Tumor-bearing mice were given anti-PD1 antibody or IgG as a control on the indicated days for a total of five treatments. (D) Excised tumors collected on day 19. (E) Representative graph showing the calculated tumor volume at the indicated time points. (F) The tumor weights of excised tumors were measured at the end of the experiment. (G) Representative graph showing the content of MDA in the tumors collected at day 19. (H) PRMT5 inhibitors in combination with anti-PD1 significantly decreased the translation of KEAP1 and increased the production of NRF2 and HMOX1 at the protein level in the indicated tumor tissues. (I) The HMOX1 expression-related survival curves of patients with cancer who received immunotherapy. (J) Expression of PRMT5, NRF2 and HMOX1 protein in human specimens derived from eight patients with TNBC who received immunotherapy. *p<0.05. CR, complete response; IFN, interferon; PD, progressive disease; PR, partial response; PRMT5, protein arginine methyltransferase 5; SD, stable disease.