{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T07:55:56Z","timestamp":1768636556945,"version":"3.49.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clinical use of immune-checkpoints inhibitors (anti PD-1\/PD-L1) resulted very effective for the treatment of relapsed\/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains (TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. TIGIT expression in T lymphocytes surrounding Hodgkin Reed-Sternberg (HRS) cells was observed in 19\/34 patients (56%), of which 11 (58%) had advanced stages. In 16\/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT\u2212 patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1\u2212. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4\/19) were PD-L1\u2212. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints\u2019 modulation. These results pave the way to new therapeutic strategies for relapsed\/refractory CHL.<\/jats:p>","DOI":"10.1038\/s41598-021-86655-8","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T10:03:03Z","timestamp":1617012183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A novel scoring system for TIGIT expression in classic Hodgkin lymphoma"],"prefix":"10.1038","volume":"11","author":[{"given":"Ombretta","family":"Annibali","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Grifoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Tomarchio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariantonietta","family":"Tafuri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Verri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Avvisati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Crescenzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"86655_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10060204","author":"N Meti","year":"2018","unstructured":"Meti, N., Esfahani, K. & Johnson, N. 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Y. & Grogan, J. L. TIGIT: A key inhibitor of the cancer immunity cycle. Trends Immunol. 38, 20\u201328. https:\/\/doi.org\/10.1016\/j.it.2016.10.002 (2017).","journal-title":"Trends Immunol."},{"key":"86655_CR7","unstructured":"Rodriguez-Abreu, D. et al. Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE) [ASCO 2020 Abstract #9503]."},{"key":"86655_CR8","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1186\/s12885-018-5111-1","volume":"18","author":"W Li","year":"2018","unstructured":"Li, W. et al. Expression of the immune checkpoint receptor TIGIT in Hodgkin\u2019s lymphoma. BMC Cancer 18, 1209. https:\/\/doi.org\/10.1186\/s12885-018-5111-1 (2018).","journal-title":"BMC Cancer"},{"issue":"5","key":"86655_CR9","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1200\/JCO.2006.09.2403","volume":"25","author":"BD Cheson","year":"2007","unstructured":"Cheson, B. D. et al. International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J. Clin. Oncol. 25(5), 579\u2013586. https:\/\/doi.org\/10.1200\/JCO.2006.09.2403 (2007).","journal-title":"J. Clin. Oncol."},{"key":"86655_CR10","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1038\/modpathol.2009.54","volume":"22","author":"SH Nam-Cha","year":"2009","unstructured":"Nam-Cha, S. H. et al. Lymphocyte-rich classical Hodgkin\u2019s lymphoma: Distinctive tumor and microenvironment markers. Mod. Pathol. 22, 1006\u20131015. https:\/\/doi.org\/10.1038\/modpathol.2009.54 (2009).","journal-title":"Mod. 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