{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:17:04Z","timestamp":1789690624043,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"DBT\/Wellcome Trust India Alliance","doi-asserted-by":"publisher","award":["IA\/I\/19\/1\/504277"],"award-info":[{"award-number":["IA\/I\/19\/1\/504277"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009053","name":"DBT\/Wellcome Trust India Alliance","doi-asserted-by":"publisher","award":["CRG\/2019\/001334"],"award-info":[{"award-number":["CRG\/2019\/001334"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["IA\/I\/19\/1\/504277"],"award-info":[{"award-number":["IA\/I\/19\/1\/504277"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CRG\/2019\/001334"],"award-info":[{"award-number":["CRG\/2019\/001334"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Multidisciplinary Research Unit (MRU), IPGME&amp;R, Kolkata","award":["IA\/I\/19\/1\/504277"],"award-info":[{"award-number":["IA\/I\/19\/1\/504277"]}]},{"name":"Multidisciplinary Research Unit (MRU), IPGME&amp;R, Kolkata","award":["CRG\/2019\/001334"],"award-info":[{"award-number":["CRG\/2019\/001334"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intravesical immunotherapy with Bacillus Calmette\u2013Guerin (BCG) is a standard of care therapy for non-muscle invasive bladder cancer (NMIBC), which accounts for about 75% of newly diagnosed urothelial cancer. However, given the frequent recurrence and progression, identification of a pre-treatment biomarker capable of predicting responsiveness to BCG in NMIBC is of utmost importance. Herein, using multiparametric flow cytometry, we characterized CD8+ T cells from peripheral blood and tumor tissues collected from 27 pre-BCG patients bearing NMIBC to obtain immune correlates of bladder cancer prognosis and responsiveness to BCG therapy. We observed that intratumoral CD8+ T cell subsets were highly heterogenous in terms of their differentiation state and exist at different proportions in tumor tissues. Remarkably, among the different CD8+ T cell subsets present in the tumor tissues, the frequency of the terminally exhausted-like CD8+ T cell subset, marked as PD1+CD38+Tim3+ CD8+ T cells, was inversely correlated with a favorable outcome for patients and a responsiveness to BCG therapy. Moreover, we also noted that the intratumoral abundance of the progenitor exhausted-like PD1+CD8+ T cell subset in pre-BCG NMIBC tumor tissues was indicative of better recurrence-free survival after BCG. Collectively, our study led to the identification of biomarkers that can predict the therapeutic responsiveness of BCG in NMIBC.<\/jats:p>","DOI":"10.3390\/cells12151939","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:50:37Z","timestamp":1690422637000},"page":"1939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intratumoral PD1+CD38+Tim3+ CD8+ T Cells in Pre-BCG Tumor Tissues Are Associated with Poor Responsiveness to BCG Immunotherapy in Patients with Non-Muscle Invasive Bladder Cancer"],"prefix":"10.3390","volume":"12","author":[{"given":"Debashree","family":"Basak","sequence":"first","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5023-7773","authenticated-orcid":false,"given":"Soumya","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Urology, IPGME&R and SSKM Hospital, Kolkata 700020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swadeep Kumar","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Urology, IPGME&R and SSKM Hospital, Kolkata 700020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborpita","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishita","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanya","family":"Basu","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Bhoumik","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7114-4656","authenticated-orcid":false,"given":"Snehanshu","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip Kumar","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Urology, IPGME&R and SSKM Hospital, Kolkata 700020, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8428-6434","authenticated-orcid":false,"given":"Shilpak","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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