{"id":246,"date":"2025-04-01T00:08:47","date_gmt":"2025-04-01T00:08:47","guid":{"rendered":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/?post_type=service&#038;p=246"},"modified":"2025-07-21T03:32:08","modified_gmt":"2025-07-21T03:32:08","slug":"paper-8","status":"publish","type":"service","link":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/publication\/paper-8\/","title":{"rendered":"Int. Immunol. 2022 (Tatsuguchi, Uruno et al.)"},"content":{"rendered":"\n<p>Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells.<\/p>\n\n\n\n<p><strong>Tatsuguchi T<\/strong>, <strong>Uruno T<\/strong>, Sugiura Y, <strong>Sakata D<\/strong>, Izumi Y, <strong>Sakurai T<\/strong>, Hattori Y, Oki E, Kubota N, Nishimoto K, Oyama M, <strong>Kunimura K<\/strong>, Ohki T, Bamba T, Tahara H, Sakamoto M, Nakamura M, Suematsu M, <strong>Fukui Y<\/strong>:<\/p>\n\n\n\n<p><strong>International Immunology<\/strong> 34(5): 277-289, <strong>2022<\/strong>.<\/p>\n\n\n\n<p>Effective tumor immunotherapy requires physical contact of T cells with cancer cells. However, tumors often constitute a specialized microenvironment that excludes T cells from the vicinity of cancer cells, and its underlying mechanisms are still poorly understood. DOCK2 is a Rac activator critical for migration and activation of lymphocytes. We herein show that cancer-derived cholesterol sulfate (CS), a lipid product of the sulfotransferase SULT2B1b, acts as a DOCK2 inhibitor and prevents tumor infiltration by effector T cells. Using clinical samples, we found that CS was abundantly produced in certain types of human cancers such as colon cancers. Functionally, CS-producing cancer cells exhibited resistance to cancer-specific T-cell transfer and immune checkpoint blockade. Although SULT2B1b is known to sulfate oxysterols and inactivate their tumor-promoting activity, the expression levels of cholesterol hydroxylases, which mediate oxysterol production, are low in SULT2B1b-expressing cancers. Therefore, SULT2B1b inhibition could be a therapeutic strategy to disrupt tumor immune evasion in oxysterol-non-producing cancers. Thus, our findings define a previously unknown mechanism for tumor immune evasion and provide a novel insight into the development of effective immunotherapies.<\/p>\n\n\n\n<p><a href=\"https:\/\/researchmap.jp\/-kunimura-\/published_papers\/36294693\">https:\/\/researchmap.jp\/-kunimura-\/published_papers\/36294693<\/a><\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"975\" src=\"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/wp-content\/uploads\/2025\/07\/\u30b9\u30af\u30ea\u30fc\u30f3\u30b7\u30e7\u30c3\u30c8-2025-07-03-12\u306e\u30b3\u30d4\u30fc.34.54-1024x975.jpg\" alt=\"\" class=\"wp-image-247\" style=\"width:421px;height:auto\" srcset=\"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/wp-content\/uploads\/2025\/07\/\u30b9\u30af\u30ea\u30fc\u30f3\u30b7\u30e7\u30c3\u30c8-2025-07-03-12\u306e\u30b3\u30d4\u30fc.34.54-1024x975.jpg 1024w, https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/wp-content\/uploads\/2025\/07\/\u30b9\u30af\u30ea\u30fc\u30f3\u30b7\u30e7\u30c3\u30c8-2025-07-03-12\u306e\u30b3\u30d4\u30fc.34.54-300x286.jpg 300w, https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/wp-content\/uploads\/2025\/07\/\u30b9\u30af\u30ea\u30fc\u30f3\u30b7\u30e7\u30c3\u30c8-2025-07-03-12\u306e\u30b3\u30d4\u30fc.34.54-768x731.jpg 768w, https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/wp-content\/uploads\/2025\/07\/\u30b9\u30af\u30ea\u30fc\u30f3\u30b7\u30e7\u30c3\u30c8-2025-07-03-12\u306e\u30b3\u30d4\u30fc.34.54-1536x1462.jpg 1536w, https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp\/wp-content\/uploads\/2025\/07\/\u30b9\u30af\u30ea\u30fc\u30f3\u30b7\u30e7\u30c3\u30c8-2025-07-03-12\u306e\u30b3\u30d4\u30fc.34.54.jpg 1544w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n","protected":false},"featured_media":247,"template":"","service_category":[8],"class_list":["post-246","service","type-service","status-publish","has-post-thumbnail","hentry","service_category-original-paper"],"_links":{"self":[{"href":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp-json\/wp\/v2\/service\/246","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp-json\/wp\/v2\/service"}],"about":[{"href":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp-json\/wp\/v2\/types\/service"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp-json\/wp\/v2\/media\/247"}],"wp:attachment":[{"href":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp-json\/wp\/v2\/media?parent=246"}],"wp:term":[{"taxonomy":"service_category","embeddable":true,"href":"https:\/\/bioreg.kyushu-u.ac.jp\/labo\/iden\/wp-json\/wp\/v2\/service_category?post=246"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}