{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:07:09Z","timestamp":1779800829495,"version":"3.53.1"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012128","name":"Austin Medical Research Foundation","doi-asserted-by":"publisher","award":["2\u20101461"],"award-info":[{"award-number":["2\u20101461"]}],"id":[{"id":"10.13039\/100012128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008018","name":"Victorian Cancer Agency","doi-asserted-by":"publisher","award":["MCRF23026"],"award-info":[{"award-number":["MCRF23026"]}],"id":[{"id":"10.13039\/100008018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021954","name":"Tour de Cure","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021954","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Gamma\u2010delta (\u03b3\u03b4) T\u00a0cells have been associated with favorable prognoses across several malignancies, underscoring their potential as targets for novel immunotherapies. These unconventional T lymphocytes exhibit an intrinsic tropism for the tumor microenvironment, largely driven by their capacity to recognize stress\u2010induced antigens characteristic of metabolically dysregulated tumors. Unlike the mechanism governing conventional cytotoxic CD8\n                      <jats:sup>+<\/jats:sup>\n                      alpha\u2010beta (\u03b1\u03b2) T\u00a0cells, \u03b3\u03b4 T\u2010cell receptors can engage tumor cell moieties independent of major histocompatibility complex class\u2010I (MHC\u2010I) and human leukocyte class\u2010I molecules. Therefore, \u03b3\u03b4 T\u00a0cells may have a pivotal role in the immune response to beta\u20102 microglobulin\u2010mutated MHC\u2010I negative (MHC\u2010I\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) colorectal cancers (CRCs) with deficient mismatch repair.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To determine whether \u03b3\u03b4 T\u2010cell mobilisation extends to diverse aetiologies of MHC\u2010I loss, we used multispectral immunohistochemistry to stain 150 stage I\u2010IV primary CRC tissues, across eight tissue microarrays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our investigation revealed MHC\u2010I loss in ~30% of CRC primary tumors across all disease stages, with a notable increase in stromal \u03b3\u03b4 T\u2010cell frequency and activation status among stage III cases. Importantly, these findings extend previous observations largely confined to mismatch repair\u2013deficient CRC by demonstrating that stromal \u03b3\u03b4 T\u2010cell enrichment associated with MHC\u2010I loss also occurs in mismatch repair\u2013proficient tumors, suggesting a broader role for \u03b3\u03b4 T\u00a0cells in immune surveillance of MHC\u2010I\u2013deficient CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These data highlight the potential of \u03b3\u03b4 T\u00a0cells in counteracting immune evasive MHC\u2010I\n                      <jats:sup>\u2212<\/jats:sup>\n                      tumors, thereby offering a robust rationale for their strategic deployment in next\u2010generation immunotherapy regimens.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70097","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:20:11Z","timestamp":1778574011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterisation of tumor\u2010infiltrating gamma\u2010delta T\u00a0cells in human colorectal cancer with MHC\u2010I loss"],"prefix":"10.1002","volume":"15","author":[{"given":"Tianming A","family":"Li","sequence":"first","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"},{"name":"School of Cancer Medicine La Trobe University  Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke T","family":"Quigley","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"},{"name":"School of Cancer Medicine La Trobe University  Heidelberg VIC Australia"},{"name":"Department of Cancer Medicine, School of Translational Medicine Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kok Fei","family":"Chan","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Williams","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"},{"name":"School of Cancer Medicine La Trobe University  Heidelberg VIC Australia"},{"name":"Department of Pathology Austin Health  Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Mielke","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"},{"name":"School of Cancer Medicine La Trobe University  Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Behren","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"},{"name":"School of Cancer Medicine La Trobe University  Heidelberg VIC Australia"},{"name":"Department of Medicine University of Melbourne  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-5204","authenticated-orcid":false,"given":"Jessica","family":"Da Gama Duarte","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg VIC Australia"},{"name":"School of Cancer Medicine La Trobe University  Heidelberg VIC Australia"},{"name":"Department of Cancer Medicine, School of Translational Medicine Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30422-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.76.9901"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02107"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.3_suppl.9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00197-8"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2009.03392.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604867"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110754"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101567"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.10.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24673"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00634-7"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.03.006"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(99)00179-2"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-002-0332-0"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00558.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2006.11.082"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604715"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-009-0765-9"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-454"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14514"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.4081\/ejh.2019.3028"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3655"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyac268"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.18.00321"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.07.019"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.3384"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.028"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0987"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1604958"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01062-w"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0593"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-23-0139"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3909"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adf2163"},{"key":"e_1_2_11_39_1","article-title":"Distinctive features of tumor\u2010infiltrating \u03b3\u03b4 T lymphocytes in human colorectal cancer","volume":"6","author":"Meraviglia S","year":"2017","journal-title":"Onco Targets Ther"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05593-1"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.894315"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00376-z"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00690-0"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03321-w"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay5516"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0153-5"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.04.004"},{"key":"e_1_2_11_48_1","article-title":"Characteristics and significance of \u03b3\u03b4 T\u00a0cells in colorectal cancer","volume":"14","author":"Karjalainen H","year":"2025","journal-title":"Onco Targets Ther"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315664"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0496-1"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30789-X"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-1327"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6204"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-00948-9"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000410"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003156"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.37349\/ei.2022.00057"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.70097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.70097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.70097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T12:43:39Z","timestamp":1779799419000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.70097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":56,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/cti2.70097"],"URL":"https:\/\/doi.org\/10.1002\/cti2.70097","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70097"}}