Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy

Abstract Objectives A diverse intratumoral T‐cell receptor (TCR) repertoire is associated with improved survival in diffuse large B‐cell lymphoma (DLBCL) treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy. We explored the impact of intratumoral T...

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Autores principales:	Mohamed Shanavas, Soi‐Cheng Law, Mark Hertzberg, Rodney J Hicks, John F Seymour, Zhixiu Li, Lilia Merida de Long, Karthik Nath, Muhammed B Sabdia, Jay Gunawardana, Maher K Gandhi, Colm Keane
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	immunotherapy interim PET lymphoma TCR repertoire Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/50bba13efe444391a61f0d8ffaa50fb2
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spelling	oai:doaj.org-article:50bba13efe444391a61f0d8ffaa50fb22021-11-25T13:32:30ZIntratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy2050-006810.1002/cti2.1351https://doaj.org/article/50bba13efe444391a61f0d8ffaa50fb22021-01-01T00:00:00Zhttps://doi.org/10.1002/cti2.1351https://doaj.org/toc/2050-0068Abstract Objectives A diverse intratumoral T‐cell receptor (TCR) repertoire is associated with improved survival in diffuse large B‐cell lymphoma (DLBCL) treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy. We explored the impact of intratumoral TCR repertoire on interim PET (iPET) done after four cycles of R‐CHOP, the relationships between intratumoral and circulating repertoire, and the phenotypes of expanded clonotypes. Methods We sequenced the third complementarity‐determining region of TCRβ in tumor samples, blood at pre‐therapy and after four cycles of R‐CHOP in 35 patients enrolled in ALLGNHL21 trial in high‐risk DLBCL. We correlated the TCR diversity metrics with iPET status, gene expression profiles and HLA‐class I genotypes. We then sequenced the FACS‐sorted peripheral blood T cells in six patients, and pentamer‐sorted EBV‐specific CD8+ T cells in one patient from this cohort. Results Compared with iPET− patients, the intratumoral TCR repertoire in iPET+ patients was characterised by higher cumulative frequency of abundant clonotypes and higher productive clonality. There was a variable overlap between circulating and intratumoral repertoires, with the dominant intratumoral clonotypes more likely to be detected in the blood. The majority of shared clonotypes were CD8+ PD‐1HI T cells, and CD8+ T cells had the largest clonal expansions in tumor and blood. In a patient with EBV+ DLBCL, EBV‐specific intratumoral clonotypes were trackable in the blood. Conclusion This study demonstrates that clonally expanded intratumoral TCR repertoires are associated with iPET+ and that the blood can be used to track tumor‐associated antigen‐specific clonotypes. These findings assist the rationale design and therapeutic monitoring of immunotherapeutic strategies in DLBCL.Mohamed ShanavasSoi‐Cheng LawMark HertzbergRodney J HicksJohn F SeymourZhixiu LiLilia Merida de LongKarthik NathMuhammed B SabdiaJay GunawardanaMaher K GandhiColm KeaneWileyarticleimmunotherapyinterim PETlymphomaTCR repertoireImmunologic diseases. AllergyRC581-607ENClinical & Translational Immunology, Vol 10, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunotherapy interim PET lymphoma TCR repertoire Immunologic diseases. Allergy RC581-607
spellingShingle	immunotherapy interim PET lymphoma TCR repertoire Immunologic diseases. Allergy RC581-607 Mohamed Shanavas Soi‐Cheng Law Mark Hertzberg Rodney J Hicks John F Seymour Zhixiu Li Lilia Merida de Long Karthik Nath Muhammed B Sabdia Jay Gunawardana Maher K Gandhi Colm Keane Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy
description	Abstract Objectives A diverse intratumoral T‐cell receptor (TCR) repertoire is associated with improved survival in diffuse large B‐cell lymphoma (DLBCL) treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy. We explored the impact of intratumoral TCR repertoire on interim PET (iPET) done after four cycles of R‐CHOP, the relationships between intratumoral and circulating repertoire, and the phenotypes of expanded clonotypes. Methods We sequenced the third complementarity‐determining region of TCRβ in tumor samples, blood at pre‐therapy and after four cycles of R‐CHOP in 35 patients enrolled in ALLGNHL21 trial in high‐risk DLBCL. We correlated the TCR diversity metrics with iPET status, gene expression profiles and HLA‐class I genotypes. We then sequenced the FACS‐sorted peripheral blood T cells in six patients, and pentamer‐sorted EBV‐specific CD8+ T cells in one patient from this cohort. Results Compared with iPET− patients, the intratumoral TCR repertoire in iPET+ patients was characterised by higher cumulative frequency of abundant clonotypes and higher productive clonality. There was a variable overlap between circulating and intratumoral repertoires, with the dominant intratumoral clonotypes more likely to be detected in the blood. The majority of shared clonotypes were CD8+ PD‐1HI T cells, and CD8+ T cells had the largest clonal expansions in tumor and blood. In a patient with EBV+ DLBCL, EBV‐specific intratumoral clonotypes were trackable in the blood. Conclusion This study demonstrates that clonally expanded intratumoral TCR repertoires are associated with iPET+ and that the blood can be used to track tumor‐associated antigen‐specific clonotypes. These findings assist the rationale design and therapeutic monitoring of immunotherapeutic strategies in DLBCL.
format	article
author	Mohamed Shanavas Soi‐Cheng Law Mark Hertzberg Rodney J Hicks John F Seymour Zhixiu Li Lilia Merida de Long Karthik Nath Muhammed B Sabdia Jay Gunawardana Maher K Gandhi Colm Keane
author_facet	Mohamed Shanavas Soi‐Cheng Law Mark Hertzberg Rodney J Hicks John F Seymour Zhixiu Li Lilia Merida de Long Karthik Nath Muhammed B Sabdia Jay Gunawardana Maher K Gandhi Colm Keane
author_sort	Mohamed Shanavas
title	Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy
title_short	Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy
title_full	Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy
title_fullStr	Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy
title_full_unstemmed	Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy
title_sort	intratumoral t‐cell receptor repertoire is predictive of interim pet scan results in patients with diffuse large b‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (r‐chop) chemoimmunotherapy
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/50bba13efe444391a61f0d8ffaa50fb2
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Intratumoral T‐cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B‐cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R‐CHOP) chemoimmunotherapy

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