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High rates of complete therapeutic responses to antibody-mediated immune checkpoint blockade, even in relapsed\/refractory patients, suggest the existence of a T\u00a0cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed immune microenvironment. We asked whether clonally expanded T cells (1)\u00a0were detectable in cHL lymph nodes, (2) showed characteristic immune phenotypes, and (3)\u00a0were inhibited by immune checkpoint molecule expression. We applied high-dimensional FACS index sorting and single cell T\u00a0cell receptor \u03b1\u03b2 sequencing to lymph node-infiltrating T cells from 10 treatment-na\u00efve patients. T\u00a0cells were predominantly CD4<jats:sup>+<\/jats:sup> and showed memory differentiation. Expression of classical immune checkpoint molecules (CTLA-4, PD-1, TIM-3) was generally low (&lt;\u200912.0% of T cells) and not different between CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells. Degrees of clonal T cell expansion varied between patients (range: 1\u201318 expanded clones per patient) and was almost exclusively restricted to CD8<jats:sup>+<\/jats:sup> T cells. Clonally expanded T cells showed non-na\u00efve phenotypes and low checkpoint molecule expression similar to non-expanded T cells. Our data suggest that the therapeutic effects of immune checkpoint blockade require mechanisms in addition to dis-inhibition of pre-existing lymphoma-directed T cell responses. Future studies on immune checkpoint blockade-associated effects will identify molecular T\u00a0cell targets, address dynamic aspects of cell compositions over time, and extend their focus beyond lymph node-infiltrating T cells.<\/jats:p>","DOI":"10.1007\/s00262-022-03264-8","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T12:02:40Z","timestamp":1660132960000},"page":"515-521","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immune phenotypes and checkpoint molecule expression of clonally expanded lymph node-infiltrating T cells in classical Hodgkin lymphoma"],"prefix":"10.1007","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-4973","authenticated-orcid":false,"given":"Alexej","family":"Ballhausen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amin","family":"Ben Hamza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Welters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Dietze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Bullinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Peter","family":"Rahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin-Leo","family":"Hansmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-0128","authenticated-orcid":false,"given":"Leo","family":"Hansmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"issue":"Suppl 1","key":"3264_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/annonc\/13.s1.11","volume":"13","author":"R Kuppers","year":"2002","unstructured":"Kuppers R, Schwering I, Brauninger A, Rajewsky K, Hansmann ML (2002) Biology of Hodgkin\u2019s lymphoma. 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All other authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Goethe-University Frankfurt am Main, Germany (<i>Ethik-Kommission der Goethe-Universit\u00e4t Frankfurt am Main<\/i>, project UCT -03\u20132016). Written informed consent was obtained from all patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}