DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Tae Woo | ko |
dc.contributor.author | Kim, Yujin | ko |
dc.contributor.author | Keum, Hyeongseop | ko |
dc.contributor.author | Jung, Wonsik | ko |
dc.contributor.author | Kang, Minho | ko |
dc.contributor.author | Jon, Sangyong | ko |
dc.date.accessioned | 2022-07-26T01:00:34Z | - |
dc.date.available | 2022-07-26T01:00:34Z | - |
dc.date.created | 2022-07-26 | - |
dc.date.created | 2022-07-26 | - |
dc.date.created | 2022-07-26 | - |
dc.date.issued | 2022-09 | - |
dc.identifier.citation | MOLECULAR THERAPY-ONCOLYTICS, v.26, pp.1 - 14 | - |
dc.identifier.issn | 2372-7705 | - |
dc.identifier.uri | http://hdl.handle.net/10203/297450 | - |
dc.description.abstract | Patients with BRAF(V600E)-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(STAT3)-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(STAT3)-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(STAT3)-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(+) 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. | - |
dc.language | English | - |
dc.publisher | CELL PRESS | - |
dc.title | Combination of a STAT3 inhibitor with anti-PD-1 immunotherapy is an effective treatment regimen for a vemurafenib-resistant melanoma | - |
dc.type | Article | - |
dc.identifier.wosid | 000824434800001 | - |
dc.identifier.scopusid | 2-s2.0-85132239080 | - |
dc.type.rims | ART | - |
dc.citation.volume | 26 | - |
dc.citation.beginningpage | 1 | - |
dc.citation.endingpage | 14 | - |
dc.citation.publicationname | MOLECULAR THERAPY-ONCOLYTICS | - |
dc.identifier.doi | 10.1016/j.omto.2022.06.001 | - |
dc.contributor.localauthor | Jon, Sangyong | - |
dc.contributor.nonIdAuthor | Kim, Yujin | - |
dc.contributor.nonIdAuthor | Kang, Minho | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | immunotherapy | - |
dc.subject.keywordAuthor | melanoma | - |
dc.subject.keywordAuthor | STAT3 inhibitors | - |
dc.subject.keywordAuthor | tumor microenvironment | - |
dc.subject.keywordAuthor | vemurafenib | - |
dc.subject.keywordPlus | CANCER DRUG-RESISTANCE | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | SUPPRESSOR-CELLS | - |
dc.subject.keywordPlus | FEEDBACK ACTIVATION | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | BRAF | - |
dc.subject.keywordPlus | MICROENVIRONMENT | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | OVERCOME | - |
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