{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T01:32:53Z","timestamp":1769650373144,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunotherapy of musculoskeletal tumors remains clinically challenging and requires the development of gene\u2010engineered\/adoptive exogenous immune cells or the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Recently, endogenous B\u2010cell infiltration into tumor microenvironments appears to be an essential promising prognostic factor controlling tumor progression in musculoskeletal malignancy. Here, we explored the level of T\u2010cell infiltration by analyzing expression profiles of CD3E, CD4, and CD8A in 1366 patients and 23 histological types. The data revealed that CD3E and CD8A expressions were predominantly inhibited in bone tumors when compared with normal bone. CD4 expression was upregulated in limited types of tumors, including chondrosarcoma\u00a0and giant cell tumor of bone, whereas other tumors demonstrated relatively lower expressions. Similarly, regarding soft tissue sarcoma, the expression of T\u2010cell\u2010related molecules was\u00a0largely inhibited. Only in patients with rhabdomyosarcoma, CD3E and CD8A expressions were significantly upregulated, showing the\u00a0nature of immune\u2010active tumor. To visualize the immunological microenvironment of rhabdomyosarcoma, we have developed a novel software aimed at analyzing numerous cell\u2010to\u2010cell and ligand\u2010to\u2010receptor interactions, that is,\u00a0Environmentome. It has led to the identification of molecular interactions between CD8<jats:sup>+<\/jats:sup> T cell and rhabdomyosarcoma via Galectin3\u2010LAG3 binding, which is a novel immune checkpoint\u00a0recently identified. In conclusion, musculoskeletal tumors may be defined as immune\u2010quiescent tumors, whereby targeting Galectin\u20103 and\/or immune\u2010infiltrative agents could be crucial in these immunologically noninflamed musculoskeletal tumors, accelerating immunotherapeutic response.<\/jats:p>","DOI":"10.1002\/jor.24890","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T17:11:10Z","timestamp":1603473070000},"page":"536-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["T\u2010cell infiltration profile in musculoskeletal tumors"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4352-7817","authenticated-orcid":false,"given":"Kosei","family":"Nakajima","sequence":"first","affiliation":[{"name":"Division of Translational Research, Exploratory Oncology Research &amp; Clinical Trial Center National Cancer Center  Chuo\u2010ku Tokyo Japan"},{"name":"Division of Veterinary Oncology and Surgery,\u00a0Faculty of Veterinary Medicine, Imabari Campus Okayama University of Science  Imabari Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Raz","sequence":"additional","affiliation":[{"name":"Department\u00a0of Oncology Karmanos Cancer Institute  Detroit Michigan USA"},{"name":"Department\u00a0of Pathology Karmanos Cancer Institute  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1793"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2014.09.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.0017"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2014.0053"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq209"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq223"},{"key":"e_1_2_8_8_1","first-page":"17","article-title":"Immunotherapy in soft\u2010tissue sarcoma","volume":"27","author":"Ayodele O","year":"2020","journal-title":"Curr\u00a0Oncol\u00a0(Toronto, 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