{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:00:08Z","timestamp":1792929608435,"version":"4.5.0"},"reference-count":69,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"747","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:p>\n                    Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell\u2013to\u2013myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells. Upon contact with tumor-experienced NK cells, monocytes and neutrophils displayed increased expression of MDSC-related suppressive factors along with increased capacities to suppress T cells. These changes were accompanied by impaired antigen presentation by monocytes and increased ER stress response by neutrophils. In a cohort of patients with sarcoma and breast cancer, the production of interleukin-6 (IL-6) by tumor-infiltrating NK cells correlated with S100A8\/9 and arginase-1 expression by MDSCs. At the same time, NK cell\u2013derived IL-6 was associated with tumors with higher major histocompatibility complex class I expression, which we further validated with\n                    <jats:italic>b2m<\/jats:italic>\n                    -knockout (KO) tumor mice models. Similarly in syngeneic wild-type and\n                    <jats:italic>IL-6<\/jats:italic>\n                    KO mouse models, we then demonstrated that the accumulation of MDSCs was influenced by the presence of such regulatory NK cells. Inhibition of the IL-6\/signal transducer and activator of transcription 3 (STAT3) axis alleviated suppression of T cell responses, resulting in reduced tumor growth and metastatic dissemination. Together, these results characterize a critical NK cell\u2013mediated mechanism that drives the development of MDSCs during tumor immune escape.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adi2952","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T13:58:51Z","timestamp":1715781531000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":91,"title":["Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6\/STAT3 axis"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1056-6134","authenticated-orcid":true,"given":"Shi Yong","family":"Neo","sequence":"first","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden."},{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Republic of Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-8255","authenticated-orcid":true,"given":"Le","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni","family":"Chong","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Republic of Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4864-1870","authenticated-orcid":true,"given":"Xu","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17165 Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-1213","authenticated-orcid":true,"given":"Mariana M. 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