biostudies-literatureChatterjee BCSIR - Indian Institute of Chemical Biology220https://www.ebi.ac.uk/biostudies/studies/S-EPMC12119415biostudies-literatureUnknown82(1)Tumor-associated macrophages (TAMs) are known to be involved in the manifestation of aggressive and therapy-resistant phenotypes in solid tumors. Nevertheless, the effects of dynamic intervention by TAMs on the DNA damage response of cancer cells are largely unexplored. Herein, we report that TAMs modulate the DNA damage repair pathways of ovarian cancer cells in response to platinum-(Pt) based therapeutic regimen. We demonstrate that coculture of TAMs with cancer cells directly upregulate Pol η, along with RAD18 and REV1 of the Translesion DNA synthesis (TLS) pathway, while concurrently downregulating components of the high-fidelity nucleotide excision repair (NER) mechanism. Consequently, we observed a better survival probability, DNA repair capacity, and enrichment of stemness propertieCellular and molecular life sciences : CMLSTumor-associated macrophages contribute to cisplatin resistance via regulating Pol η-mediated translesion DNA synthesis in ovarian cancer.PMC12119415OLP-121Ganesan SKGhosh DBose SSrivastava AKMishra SChatterjee NChatterjee BSarkar MKhan MMAfalseTumor-associated macrophages contribute to cisplatin resistance via regulating Pol η-mediated translesion DNA synthesis in ovarian cancer.Tumor-associated macrophages (TAMs) are known to be involved in the manifestation of aggressive and therapy-resistant phenotypes in solid tumors. Nevertheless, the effects of dynamic intervention by TAMs on the DNA damage response of cancer cells are largely unexplored. Herein, we report that TAMs modulate the DNA damage repair pathways of ovarian cancer cells in response to platinum-(Pt) based therapeutic regimen. We demonstrate that coculture of TAMs with cancer cells directly upregulate Pol η, along with RAD18 and REV1 of the Translesion DNA synthesis (TLS) pathway, while concurrently downregulating components of the high-fidelity nucleotide excision repair (NER) mechanism. Consequently, we observed a better survival probability, DNA repair capacity, and enrichment of stemness propertie2025-01-01T00:00:00Z2025 May2026-06-02T02:41:17.265Z2026-04-13T03:13:07.012ZS-EPMC121194154043730310.1007/s00018-025-05731-8