{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:15:57Z","timestamp":1780330557149,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratory for Synthetic Chemistry and Chemical Biology","award":["T12-703\/22-R"],"award-info":[{"award-number":["T12-703\/22-R"]}]},{"name":"Laboratory for Synthetic Chemistry and Chemical Biology","award":["T12-703\/23-N"],"award-info":[{"award-number":["T12-703\/23-N"]}]},{"name":"Laboratory for Synthetic Chemistry and Chemical Biology","award":["05162186"],"award-info":[{"award-number":["05162186"]}]},{"name":"The Government of Hong Kong Special Administrative Region of the People\u2019s Republic of China","award":["T12-703\/22-R"],"award-info":[{"award-number":["T12-703\/22-R"]}]},{"name":"The Government of Hong Kong Special Administrative Region of the People\u2019s Republic of China","award":["T12-703\/23-N"],"award-info":[{"award-number":["T12-703\/23-N"]}]},{"name":"The Government of Hong Kong Special Administrative Region of the People\u2019s Republic of China","award":["05162186"],"award-info":[{"award-number":["05162186"]}]},{"name":"Health and Medical Research Fund","award":["T12-703\/22-R"],"award-info":[{"award-number":["T12-703\/22-R"]}]},{"name":"Health and Medical Research Fund","award":["T12-703\/23-N"],"award-info":[{"award-number":["T12-703\/23-N"]}]},{"name":"Health and Medical Research Fund","award":["05162186"],"award-info":[{"award-number":["05162186"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The use of immune checkpoint inhibitors (ICIs) in cancer treatment has shown promise but can also have unintended consequences, such as reactivating latent tuberculosis (TB). To develop treatments that address ICIs-related adverse events, it is essential to understand cellular heterogeneity across healthy and pathological tissues. We performed cross-tissue multiplexed staining analysis on samples from two patients with TB reactivation during pembrolizumab treatment for metastatic nasopharyngeal carcinoma. CD8+ T cells, rather than CD4+ T cells, accumulated preferentially in the tuberculoma and were associated with increased production of IFN\u03b3 and expression of CD137. Additionally, CD137 enrichment played a role in the spatial organization of the tuberculoma, with specific interaction limited to spatial proximal cells between IFN\u03b3+ CD137+ CD8+ T cells and IL12+ CD137+ type-1 macrophages. This unique feature was not observed in non-tumoral or tumoral tissues. Our analysis of public transcriptomic datasets supported the notion that this cellular interaction was more prominent in patients with durable ICI responses compared to those with non-ICI-related TB. We suggest that shifts towards CD137-rich immune niches are correlated with both off-target immune-related adverse events and anti-tumor efficacy. Targeting the tumor microenvironment through conditional activation of anti-CD137 signaling in combination with ICIs can modulate the reactivity of T cells and macrophages for localized tumor killing without the potential off-target immune-related risks associated with ICIs alone.<\/jats:p>","DOI":"10.3390\/cancers16020268","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T05:21:38Z","timestamp":1704691298000},"page":"268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Shift in Tissue-Specific Immune Niches and CD137 Expression in Tuberculoma of Pembrolizumab-Treated Nasopharyngeal Carcinoma Patients"],"prefix":"10.3390","volume":"16","author":[{"given":"Ngar Woon","family":"Kam","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Laboratory of Synthetic Chemistry and Chemical Biology Limited, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9388-310X","authenticated-orcid":false,"given":"Anthony Wing Ip","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Mary Hospital, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmond Tae Yang","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0254-3274","authenticated-orcid":false,"given":"Ho","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China"},{"name":"Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Chun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Laboratory of Synthetic Chemistry and Chemical Biology Limited, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1304-2854","authenticated-orcid":false,"given":"Dora Lai Wan","family":"Kwong","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka On","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"To Wai","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Ming","family":"Che","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic Chemistry and Chemical Biology Limited, Hong Kong 999077, China"},{"name":"Department of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6283-978X","authenticated-orcid":false,"given":"Victor Ho Fun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"},{"name":"Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.ijrobp.2004.07.702","article-title":"Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience","volume":"61","author":"Lee","year":"2005","journal-title":"Int. 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