Supplementary Figures S1-S17 from Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer
Authors: Chaudagar Kiranj , Hieromnimon Hanna M. , Khurana Rimpi , Labadie Brian , Hirz Taghreed , Mei Shenglin , Hasan Raisa , Shafran Jordan , Kelley Anne , Apostolov Eva , Al-Eryani Ghamdan , Harvey Kate , Rameshbabu Srikrishnan , Loyd Mayme , Bynoe Kaela , Drovetsky Catherine , Solanki Ani , Markiewicz Erica , Zamora Marta , Fan Xiaobing , Schürer Stephan , Swarbrick Alexander , Sykes David B. , Patnaik Akash 
Published: September 2024

<p>Supplementary Figure S1. The majority of Pb-Cre; PTENfl/fl Trp53fl/fl mice are de novo resistant to ADT.
Supplementary Figure S2. ADT/PI3Ki combination therapy halts prostate tumor growth up to 14 days, followed by development of resistance in majority of Pb-Cre; PTENfl/fl Trp53fl/fl
mice.
Supplementary Figure S3. PI3Ki treatment with concurrent androgen depletion does not alter proliferation and survival of PTEN/p53-deficient murine PC cells in vitro.
Supplementary Figure S4. ADT/PI3K inhibitor combination increases MHC-II and PD-1 expression on TAM within the TME of PTEN/p53-deficient murine PC.
Supplementary Figure S5. PD-1 upregulation suppresses phagocytic capacity of activated TAM.
Supplementary Figure S6. Ex vivo AD + PI3Ki + PD-1 antibody treatment activates MHCIIlo TAM when co-cultured with PTEN/p53-deficient murine prostate tumor cells.
Supplementary Figure S7. The addition of PD-1 blockade to androgen depletion/PI3Ki therapy does not alter phagocytic capacity of PD-1 lo macrophages.
Supplementary Figure S8. The combination of androgen depletion, PI3Ki and aPD-1 blockade does not alter phagocytic checkpoint expression on PTEN/p53-deficient prostate tumor cells.
Supplementary Figure S9. Androgen depletion, singly and in combination with aPD-1, did not alter phagocytosis activity of inactivated MHC-IIlo/PD-1 lo and MHC-IIlo/PD-1 hi TAM subsets.
Supplementary Figure S10. Androgen depletion, not PI3Ki or aPD1, directly enhances TAM activation within the TME of PTEN/p53-deficient PC.
Supplementary Figure S11. PI3Ki does not alter phagocytosis/histone lactylation status of MHC-IIlo/PD-1 lo TAM and MHC-IIlo/PD-1 hi TAM.
Supplementary Figure S12. PI3Ki inhibits lactate secretion from PTEN/p53-deficient prostate tumor cells within TME.
Supplementary Figure S13. Direct ex vivo treatment of TAM with PI3Ki, singly and in combination with PD-1 antibody and/or androgen depletion does not alter their histone lactylation profile.
Supplementary Figure S14. ADT + PI3Ki + aPD-1 induces tumor control in 60% of Pb-Cre; PTENfl/fl TP53fl/fl mice.
Supplementary Figure S15. Depletion of activated TAM abrogates anti-cancer response elicited by ADT + PI3Ki + PD-1 antibody treatment in the PTEN/p53-deficient murine prostate GEMM tumors.
Supplementary Figure S16. Long-term treatment of ADT + PI3Ki + aPD-1 activates Wnt/βcatenin pathway in murine PTEN/p53-deficient GEMM-derived SC1 cells.
Supplementary Figure S17. Feedback Wnt/β-catenin-pathway activation within murine PTEN/p53-deficient GEMM-derived PC cells following long-term ADT + copanlisib + aPD1 treatment suppresses phagocytosis via increased histone lactylation within bone marrow derived macrophages (BMDM).</p>