{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:28Z","timestamp":1787008588673,"version":"build-2736575974"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute for Cancer Vaccines and Immunotherapy","award":["PhD2015\/21"],"award-info":[{"award-number":["PhD2015\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>V\u03b42+ T cells can recognize malignantly transformed cells as well as those infected with mycobacteria. This cross-reactivity supports the idea of using mycobacteria to manipulate V\u03b42+ T cells in cancer immunotherapy. To date, therapeutic interventions using V\u03b42+ T cells in cancer have involved expanding these cells in or ex vivo using zoledronic acid (ZA). Here, we show that the mycobacterium Bacillus Calmette\u2013Gu\u00e9rin (BCG) also causes V\u03b42+ T-cell expansion in vitro and that resulting V\u03b42+ cell populations are cytotoxic toward tumour cell lines. We show that both ZA and BCG-expanded V\u03b42+ cells effectively killed both Daudi and THP-1 cells. THP-1 cell killing by both ZA and BCG-expanded V\u03b42+ cells was enhanced by treatment of targets cells with ZA. Although no difference in cytotoxic activity between ZA- and BCG-expanded V\u03b42+ cells was observed, BCG-expanded cells degranulated more and produced a more diverse range of cytokines upon tumour cell recognition compared to ZA-expanded cells. ZA-expanded V\u03b42+ cells were shown to upregulate exhaustion marker CD57 to a greater extent than BCG-expanded V\u03b42+ cells. Furthermore, ZA expansion was associated with upregulation of inhibitory markers PD-1 and TIM3 in a dose-dependent manner whereas PD-1 expression was not increased following expansion using BCG. Intradermal BCG vaccination of rhesus macaques caused in vivo expansion of V\u03b42+ cells. In combination with the aforementioned in vitro data, this finding suggests that BCG treatment could induce expansion of V\u03b42+ T cells with enhanced anti-tumour potential compared to ZA treatment and that either ZA or BCG could be used intratumourally as a means to potentiate stronger anti-tumour V\u03b42+ T-cell responses.<\/jats:p>","DOI":"10.1093\/cei\/uxac032","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T11:00:15Z","timestamp":1649674815000},"page":"301-315","source":"Crossref","is-referenced-by-count":10,"title":["Bacillus Calmette-Guerin (BCG) induces superior anti-tumour responses by V\u03b42+ T cells compared with the aminobisphosphonate drug zoledronic acid"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-7831","authenticated-orcid":false,"given":"J","family":"Fenn","sequence":"first","affiliation":[{"name":"Institute for Infection and Immunity, St. George's, University of London , London 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Dalgleish","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, St. George's, University of London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Reljic","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, St. George's, University of London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sharpe","sequence":"additional","affiliation":[{"name":"Health Security Agency UK , Porton Down , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bodman-Smith","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, St. George's, University of London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"issue":"Exp 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