{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:35:26Z","timestamp":1789864526845,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neoadjuvant cisplatin\u2010based chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle\u2010invasive bladder cancer (MIBC). Pathologic complete response (pCR) is associated with favorable outcomes, but only 30%\u201340% of patients achieve that response. The aim of this study is to investigate the role played by the Tumor and Immune Microenvironment (TIME) in association with the clinical outcome of patients with MIBC undergoing NAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Nineteen patients received NAC and were classified as pCR (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) or non\u2010pCR (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099). Bulk RNA\u2010seq and immune protein evaluations using Digital Spatial Profiling (DSP) were performed on formalin\u2010fixed paraffin\u2010embedded (FFPE) tumor biopsies collected before NAC (baseline). Immunohistochemistry (IHC) evaluation focused on CD3 and CD20 expression was performed on baseline and end\u2010of\u2010treatment (EOT) FFPEs. Baseline peripheral blood was assessed for lymphocyte and neutrophil counts. Kaplan\u2013Meier analyses and Cox PH regression models were used for survival analyses (OS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the periphery, pCR patients showed lower neutrophil counts, and neutrophil\/ lymphocyte ratio (NLR) when compared to non\u2010pCR patients. In the tumor microenvironment (TME), gene expression analysis and protein evaluations highlighted an abundance of B cells and CD3\n                      <jats:sup>+<\/jats:sup>\n                      T cells in pCR versus non\u2010pCR patients. On the contrary, increased protein expression of ARG1\n                      <jats:sup>+<\/jats:sup>\n                      cells, and cells expressing immune checkpoints such as LAG3, ICOS, and STING were observed in the TME of patients with non\u2010pCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In the current study, we demonstrated that lower NLR levels and increased CD3\n                      <jats:sup>+<\/jats:sup>\n                      T cells and B cell infiltration are associated with improved response and long\u2010term outcomes in patients with MIBC receiving NAC. These findings suggest that the impact of immune environment should be considered in determining the clinical outcome of MIBC patients treated with NAC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70088","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T06:59:15Z","timestamp":1723186755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of intra\u2010tumoral immunity on predicting response and survival after neoadjuvant cisplatin\u2010based chemotherapy in patients with muscle invasive bladder cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4849-1593","authenticated-orcid":false,"given":"Alberto","family":"Mendoza\u2010Valderrey","sequence":"first","affiliation":[{"name":"Translational Cancer Immunology and Immunotherapy Department Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"},{"name":"Rosalie and Harold Rae Brown Cancer Immunotherapy Research Program Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Urologic Oncology Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria M.","family":"Kessler","sequence":"additional","affiliation":[{"name":"Bioinformatic Department Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Urologic Oncology Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Li","sequence":"additional","affiliation":[{"name":"Technology Center for Genomics and Bioinformatics, UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kolker","sequence":"additional","affiliation":[{"name":"Pathology Department Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Allen","sequence":"additional","affiliation":[{"name":"Pathology Department Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Linehan","sequence":"additional","affiliation":[{"name":"Department of Urologic Oncology Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemyslaw W.","family":"Twardowski","sequence":"additional","affiliation":[{"name":"Department of Urologic Oncology Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8904-1613","authenticated-orcid":false,"given":"Maria Libera","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Translational Cancer Immunology and Immunotherapy Department Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"},{"name":"Rosalie and Harold Rae Brown Cancer Immunotherapy Research Program Saint John's Cancer Institute, Providence Saint John's Health Center  Santa Monica California USA"},{"name":"Translational Cancer Immunology University of Glasgow  Glasgow 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