ORCID Profile
0000-0002-2155-5203
Current Organisation
Garvan Institute of Medical Research
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Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/1078-0432.22551385.V1
Abstract: Supplementary Table S1. ADT + PI3Ki + PD-1 antibody leads to TAM activation within TME of PTEN 53-deficient prostate tumors.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/1078-0432.22551388.V1
Abstract: 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 53-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 53-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 53-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 53-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 53-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 53-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 53-deficient murine prostate GEMM tumors. Supplementary Figure S16. Long-term treatment of ADT + PI3Ki + aPD-1 activates Wnt/βcatenin pathway in murine PTEN 53-deficient GEMM-derived SC1 cells. Supplementary Figure S17. Feedback Wnt/β-catenin-pathway activation within murine PTEN 53-deficient GEMM-derived PC cells following long-term ADT + copanlisib + aPD1 treatment suppresses phagocytosis via increased histone lactylation within bone marrow derived macrophages (BMDM).
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2023
DOI: 10.1158/1078-0432.22820227.V1
Abstract: Supplementary Table S1. ADT + PI3Ki + PD-1 antibody leads to TAM activation within TME of PTEN 53-deficient prostate tumors.
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2023
DOI: 10.1158/1078-0432.22820230.V1
Abstract: 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 53-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 53-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 53-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 53-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 53-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 53-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 53-deficient murine prostate GEMM tumors.Supplementary Figure S16. Long-term treatment of ADT + PI3Ki + aPD-1 activates Wnt/βcatenin pathway in murine PTEN 53-deficient GEMM-derived SC1 cells.Supplementary Figure S17. Feedback Wnt/β-catenin-pathway activation within murine PTEN 53-deficient GEMM-derived PC cells following long-term ADT + copanlisib + aPD1 treatment suppresses phagocytosis via increased histone lactylation within bone marrow derived macrophages (BMDM).
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/1078-0432.C.6563227.V1
Abstract: AbstractPurpose: Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC. Experimental Design: Prostate-specific PTEN 53-deficient genetically engineered mice (GEM) with established 150–200 mm sup /sup tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti–PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or i ex vivo /i co-culture studies. Single-cell RNA sequencing on human mCRPC s les was performed using 10X Genomics platform. Results: Coclinical trials in PTEN 53-deficient GEM revealed that recruitment of PD-1–expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination–induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy s les revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression. Conclusions: Immunometabolic strategies that reverse lactate and PD-1–mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC. /
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2023
DOI: 10.1158/1078-0432.C.6563227.V2
Abstract: AbstractPurpose: Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC. Experimental Design: Prostate-specific PTEN 53-deficient genetically engineered mice (GEM) with established 150–200 mm sup /sup tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti–PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or i ex vivo /i co-culture studies. Single-cell RNA sequencing on human mCRPC s les was performed using 10X Genomics platform. Results: Coclinical trials in PTEN 53-deficient GEM revealed that recruitment of PD-1–expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination–induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy s les revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression. Conclusions: Immunometabolic strategies that reverse lactate and PD-1–mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/1078-0432.22551388
Abstract: 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 53-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 53-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 53-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 53-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 53-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 53-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 53-deficient murine prostate GEMM tumors. Supplementary Figure S16. Long-term treatment of ADT + PI3Ki + aPD-1 activates Wnt/βcatenin pathway in murine PTEN 53-deficient GEMM-derived SC1 cells. Supplementary Figure S17. Feedback Wnt/β-catenin-pathway activation within murine PTEN 53-deficient GEMM-derived PC cells following long-term ADT + copanlisib + aPD1 treatment suppresses phagocytosis via increased histone lactylation within bone marrow derived macrophages (BMDM).
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/1078-0432.22551385
Abstract: Supplementary Table S1. ADT + PI3Ki + PD-1 antibody leads to TAM activation within TME of PTEN 53-deficient prostate tumors.
Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2022
DOI: 10.1101/2022.08.23.505054
Abstract: FFPE (formalin-fixed, paraffin-embedded) tissue archives are the largest repository of clinically annotated human specimens. Despite numerous advances in technology, current methods for sequencing of FFPE-fixed single-cells are slow, labour intensive, insufficiently sensitive and have a low resolution, making it difficult to fully exploit their enormous research and clinical potential. Here we introduce single nuclei pathology sequencing (snPATHO-Seq), a sensitive and efficient high-throughput platform to profile the transcriptome of single nuclei extracted from formalin-fixed paraffin-embedded (FFPE) s les. snPATHO-Seq combines an optimised nuclei extraction protocol from archival s les with 10x Genomics probe-based technology targeting the whole transcriptome. We performed direct comparison of the Fixed RNA Profiling (FRP) and established 3’ single cell RNA-Sequencing (scRNA-Seq) workflows through a comprehensive bioinformatics analysis of matched fresh and fixed s les derived from the LNCaP prostate cancer cell line. FRP detected 2.1 times more transcripts in the fixed s le than the 3’ kit did in the fresh s le. Low mitochondrial genes detection using the FRP was translated into 99.9 percent of cells passing the QC filters, compared to 81.6 percent of cells using the v3.1 chemistry. We then optimized snPATHO-Seq and applied it to a human breast cancer metastasis to the liver collected at autopsy and preserved in FFPE, a particularly challenging s le type. Remarkably, at 28,000 reads/cell snPATHO-Seq was able to detect a median of 1850 genes/cell and 3,216 UMI counts/cell. Comparison of snPATHO-Seq with spatial transcriptomics data (10x Genomics Visium FFPE v1) derived from an adjacent section of the same s le revealed a strong correlation, validating the accuracy of the snPATHO-Seq data. Gene expression data from snPATHO-Seq was used to predict cell type composition within each spatial transcriptomic location via deconvolution. Overall, snPATHO-Seq enables high quality and sensitivity snRNA-Seq from preserved tissue s les, unlocking the vast archives of FFPE tissues and thereby allowing extensive retrospective clinical genomic studies.
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2023
DOI: 10.1158/1078-0432.22820227
Abstract: Supplementary Table S1. ADT + PI3Ki + PD-1 antibody leads to TAM activation within TME of PTEN 53-deficient prostate tumors.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/1078-0432.CCR-22-3350
Abstract: Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC. Prostate-specific PTEN 53-deficient genetically engineered mice (GEM) with established 150–200 mm3 tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti–PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or ex vivo co-culture studies. Single-cell RNA sequencing on human mCRPC s les was performed using 10X Genomics platform. Coclinical trials in PTEN 53-deficient GEM revealed that recruitment of PD-1–expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination–induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy s les revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression. Immunometabolic strategies that reverse lactate and PD-1–mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC.
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2023
DOI: 10.1158/1078-0432.C.6563227
Abstract: AbstractPurpose: Phosphatase and tensin homolog (PTEN) loss of function occurs in approximately 50% of patients with metastatic castrate-resistant prostate cancer (mCRPC), and is associated with poor prognosis and responsiveness to standard-of-care therapies and immune checkpoint inhibitors. While PTEN loss of function hyperactivates PI3K signaling, combinatorial PI3K/AKT pathway and androgen deprivation therapy (ADT) has demonstrated limited anticancer efficacy in clinical trials. Here, we aimed to elucidate mechanism(s) of resistance to ADT/PI3K-AKT axis blockade, and to develop rational combinatorial strategies to effectively treat this molecular subset of mCRPC. Experimental Design: Prostate-specific PTEN 53-deficient genetically engineered mice (GEM) with established 150–200 mm sup /sup tumors, as assessed by ultrasound, were treated with either ADT (degarelix), PI3K inhibitor (copanlisib), or anti–PD-1 antibody (aPD-1), as single agents or their combinations, and tumors were monitored by MRI and harvested for immune, transcriptomic, and proteomic profiling, or i ex vivo /i co-culture studies. Single-cell RNA sequencing on human mCRPC s les was performed using 10X Genomics platform. Results: Coclinical trials in PTEN 53-deficient GEM revealed that recruitment of PD-1–expressing tumor-associated macrophages (TAM) thwarts ADT/PI3Ki combination–induced tumor control. The addition of aPD-1 to ADT/PI3Ki combination led to TAM-dependent approximately 3-fold increase in anticancer responses. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation within TAM, resulting in their anticancer phagocytic activation, which was augmented by ADT/aPD-1 treatment and abrogated by feedback activation of Wnt/β-catenin pathway. Single-cell RNA-sequencing analysis in mCRPC patient biopsy s les revealed a direct correlation between high glycolytic activity and TAM phagocytosis suppression. Conclusions: Immunometabolic strategies that reverse lactate and PD-1–mediated TAM immunosuppression, in combination with ADT, warrant further investigation in patients with PTEN-deficient mCRPC. /
Publisher: Springer Science and Business Media LLC
Date: 09-2021
Publisher: Cold Spring Harbor Laboratory
Date: 06-04-2023
DOI: 10.1101/2023.04.06.535805
Abstract: Spatial transcriptomic technologies are powerful tools for resolving the spatial heterogeneity of gene expression in tissue s les. However, little evidence exists on relative strengths and weaknesses of the various available technologies for profiling human tumour tissue. In this study, we aimed to provide an objective assessment of two common spatial transcriptomics platforms, 10X Genomics’ Visium and Nanostring’s GeoMx DSP. The abilities of the DSP and Visium platforms to profile transcriptomic features were compared using matching cell line and primary breast cancer tissue s les. A head-to-head comparison was conducted using data generated from matching s les and synthetic tissue references. Platform specific features were also assessed according to manufacturers’ recommendations to evaluate the optimal usage of the two technologies. We identified substantial variations in assay design between the DSP and Visium assays such as transcriptomic coverage and composition of the transcripts detected. When the data was standardised according to manufacturers’ recommendations, the DSP platform was more sensitive in gene expression detection. However, its specificity was diminished by the presence of non-specific detection. Our results also confirmed the strength and weakness of each platform in characterising spatial transcriptomic features of tissue s les, in particular their application to hypothesis generation versus hypothesis testing. In this study, we share our experience on both DSP and Visium technologies as end users. We hope this can guide future users to choose the most suitable platform for their research. In addition, this dataset can be used as an important resource for the development of new analysis tools.
Publisher: American Association for Cancer Research (AACR)
Date: 15-05-2023
DOI: 10.1158/1078-0432.22820230
Abstract: 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 53-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 53-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 53-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 53-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 53-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 53-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 53-deficient murine prostate GEMM tumors.Supplementary Figure S16. Long-term treatment of ADT + PI3Ki + aPD-1 activates Wnt/βcatenin pathway in murine PTEN 53-deficient GEMM-derived SC1 cells.Supplementary Figure S17. Feedback Wnt/β-catenin-pathway activation within murine PTEN 53-deficient GEMM-derived PC cells following long-term ADT + copanlisib + aPD1 treatment suppresses phagocytosis via increased histone lactylation within bone marrow derived macrophages (BMDM).
No related grants have been discovered for Kate Harvey.