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However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients\u2019 samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (<jats:italic>IL12A<\/jats:italic>, <jats:italic>IL2<\/jats:italic>, <jats:italic>IL10<\/jats:italic>, <jats:italic>TGFB1<\/jats:italic>, <jats:italic>TGFBR1<\/jats:italic>, <jats:italic>TGFBR2<\/jats:italic>, <jats:italic>IL17A<\/jats:italic>, <jats:italic>IL17F<\/jats:italic>) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>High FOXP3\/CD3 ratios (<jats:italic>p<\/jats:italic>\u00a0=\u20090.001), high IL17A levels (<jats:italic>p<\/jats:italic>\u00a0=\u20090.003) and low IL2 levels (<jats:italic>p<\/jats:italic>\u00a0=\u20090.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (<jats:italic>p<\/jats:italic>\u00a0=\u20090.02). In the SNV model, the CC haplotype of <jats:italic>IL10<\/jats:italic> (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.01), the GG genotype of <jats:italic>IL2<\/jats:italic> rs2069762 (p\u2009=\u20090.02) and the AA+AG genotypes of <jats:italic>TGFBR2<\/jats:italic> rs3087465 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.01) were independent predictors of outcome. Finally, the GG genotype of <jats:italic>TGFB1<\/jats:italic> rs6957 associated with lower tumor TGF\u03b2 levels (<jats:italic>p<\/jats:italic>\u00a0=\u20090.03) and less CD163+ macrophages (<jats:italic>p<\/jats:italic>\u00a0=\u20090.01), but did not modulate patients\u2019 survival.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in <jats:italic>IL10<\/jats:italic>, <jats:italic>TGFBR2<\/jats:italic> and <jats:italic>IL2,<\/jats:italic> may represent novel prognostic factors in this disease, following future validations.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-021-07891-9","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T08:03:03Z","timestamp":1614585783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Single nucleotide variants in immune-response genes and the tumor microenvironment composition predict progression of mantle cell lymphoma"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-4159","authenticated-orcid":false,"given":"Guilherme Rossi","family":"Assis-Mendon\u00e7a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Fattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Malagoli","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Jacob","family":"Louren\u00e7o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia Torresan","family":"Delamain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suely","family":"Nonogaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladmir Cl\u00e1udio Cordeiro","family":"de Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele Wally Braga","family":"Colleoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1rmino Antonio","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Augusto","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Silvia Passos","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Vassallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"issue":"6","key":"7891_CR1","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1002\/ajh.25487","volume":"94","author":"P Jain","year":"2019","unstructured":"Jain P, Wang M. 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