{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim TW"],"funding":["Ministry of Science, ICT and Future Planning","National Research Foundation of Korea"],"pagination":["1-14"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9218293"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26"],"pubmed_abstract":["Patients with BRAF<sup>V600E</sup>-mutant melanoma are effectively treated with the BRAF-inhibiting drug, vemurafenib, but soon develop drug resistance, limiting vemurafenib's therapeutic efficacy. Constitutive activation of STAT3 in cancer cells and immune cells in the tumor microenvironment (TME) is a crucial contributor to the development of drug resistance and immune evasion in most cancers. Here, we investigated the antitumor efficacy and TME remodeling by APT<sub>STAT3</sub>-9R, a cell-permeable STAT3 inhibitory peptide, as a strategy to treat vemurafenib-resistant melanoma. We found that vemurafenib-resistant melanoma remodels into immunosuppressive TME by increasing the expression of specific chemokines to facilitate the infiltration of immunosuppressive immune cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Intratumoral treatment of APT<sub>STAT3</sub>-9R led to a reduction in the population of MDSCs and TAMs, while increasing infiltration of cytotoxic T lymphocytes in the TME. Moreover, combination therapy with APT<sub>STAT3</sub>-9R and an anti-PD-1 antibody enhanced significant suppression of tumor growth by decreasing infiltration of these immunosuppressive immune cells while increasing the infiltration and cytotoxicity of CD8<sup>+</sup> T cells. These findings suggest that combined blockade of STAT3 and PD-1 signaling pathways may be an effective treatment option for overcoming poor therapeutic outcomes associated with drug-resistant BRAF-mutant melanoma."],"journal":["Molecular therapy oncolytics"],"pubmed_title":["Combination of a STAT3 inhibitor with anti-PD-1 immunotherapy is an effective treatment regimen for a vemurafenib-resistant melanoma."],"pmcid":["PMC9218293"],"funding_grant_id":["NRF2018R1A3B1052661"],"pubmed_authors":["Kim TW","Jung W","Kang M","Kim Y","Jon S","Keum H"],"additional_accession":[]},"is_claimable":false,"name":"Combination of a STAT3 inhibitor with anti-PD-1 immunotherapy is an effective treatment regimen for a vemurafenib-resistant melanoma.","description":"Patients with BRAF<sup>V600E</sup>-mutant melanoma are effectively treated with the BRAF-inhibiting drug, vemurafenib, but soon develop drug resistance, limiting vemurafenib's therapeutic efficacy. Constitutive activation of STAT3 in cancer cells and immune cells in the tumor microenvironment (TME) is a crucial contributor to the development of drug resistance and immune evasion in most cancers. Here, we investigated the antitumor efficacy and TME remodeling by APT<sub>STAT3</sub>-9R, a cell-permeable STAT3 inhibitory peptide, as a strategy to treat vemurafenib-resistant melanoma. We found that vemurafenib-resistant melanoma remodels into immunosuppressive TME by increasing the expression of specific chemokines to facilitate the infiltration of immunosuppressive immune cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Intratumoral treatment of APT<sub>STAT3</sub>-9R led to a reduction in the population of MDSCs and TAMs, while increasing infiltration of cytotoxic T lymphocytes in the TME. Moreover, combination therapy with APT<sub>STAT3</sub>-9R and an anti-PD-1 antibody enhanced significant suppression of tumor growth by decreasing infiltration of these immunosuppressive immune cells while increasing the infiltration and cytotoxicity of CD8<sup>+</sup> T cells. These findings suggest that combined blockade of STAT3 and PD-1 signaling pathways may be an effective treatment option for overcoming poor therapeutic outcomes associated with drug-resistant BRAF-mutant melanoma.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-03-31T11:40:46.387Z","creation":"2025-02-19T04:14:14.993Z"},"accession":"S-EPMC9218293","cross_references":{"pubmed":["35784401"],"doi":["10.1016/j.omto.2022.06.001"]}}