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The identification of TCF1+ progenitor exhausted T cells in THRLBCL may predict a better response to PD-1/PD-L1 blockade.
Tabanelli, Valentina; Melle, Federica; Motta, Giovanna; Mazzara, Saveria; Fabbri, Marco; Agostinelli, Claudio; Calleri, Angelica; Del Corvo, Marcello; Fiori, Stefano; Lorenzini, Daniele; Cesano, Alessandra; Chiappella, Annalisa; Vitolo, Umberto; Derenzini, Enrico; Griffin, Gabriel K; Rodig, Scott J; Vanazzi, Anna; Sabattini, Elena; Tarella, Corrado; Sapienza, Maria Rosaria; Pileri, Stefano A.
Afiliação
  • Tabanelli V; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Melle F; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Motta G; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Mazzara S; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Fabbri M; European Commission, Joint Research Centre (JRC), Ispra, Italy.
  • Agostinelli C; Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  • Calleri A; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Del Corvo M; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Fiori S; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Lorenzini D; Division of Haematopathology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Cesano A; NanoString Technologies, Inc., Seattle, WA.
  • Chiappella A; ESSA Pharma, South San Francisco, CA.
  • Vitolo U; Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Derenzini E; Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-IRCCS, Candiolo, Italy.
  • Griffin GK; Onco-Hematology Unit, European Institute of Oncology, IRCCS, Milan, Italy.
  • Rodig SJ; Department of Health Sciences, University of Milan, Milan, Italy.
  • Vanazzi A; Department of Pathology, Dana-Farber Cancer Institute, Boston, MA; and.
  • Sabattini E; Department of Pathology, Brigham and Women's Hospital, Boston, MA.
  • Tarella C; Onco-Hematology Unit, European Institute of Oncology, IRCCS, Milan, Italy.
  • Sapienza MR; Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  • Pileri SA; Onco-Hematology Unit, European Institute of Oncology, IRCCS, Milan, Italy.
Blood Adv ; 6(15): 4634-4644, 2022 08 09.
Article em En | MEDLINE | ID: mdl-35767735
ABSTRACT
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of diffuse large B-cell lymphoma (DLBCL) that usually affects young to middle-aged patients, with disseminated disease at presentation. The tumor microenvironment (TME) plays a key role in THRLBCL due to its peculiar cellular composition (<10% neoplastic B cells interspersed in a cytotoxic T-cell/histiocyte-rich background). A significant percentage of THRLBCL is refractory to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-based regimens and to chimeric antigen receptor T-cell therapy; thus, the development of a specific therapeutic approach for these patients represents an unmet clinical need. To better understand the interaction of immune cells in THRLBCL TME and identify more promising therapeutic strategies, we compared the immune gene expression profiles of 12 THRLBCL and 10 DLBCL samples, and further corroborated our findings in an extended in silico set. Gene coexpression network analysis identified the predominant role of the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis in the modulation of the immune response. Furthermore, the PD-1/PD-L1 activation was flanked by the overexpression of 48 genes related to the functional exhaustion of T cells. Globally, THRLBCL TME was highly interferon-inflamed and severely exhausted. The immune gene profiling findings strongly suggest that THRLBCL may be responsive to anti-PD-1 therapy but also allowed us to take a step forward in understanding THRLBCL TME. Of therapeutic relevance, we validated our results by immunohistochemistry, identifying a subset of TCF1+ (T cell-specific transcription factor 1, encoded by the TCF7 gene) progenitor exhausted T cells enriched in patients with THRLBCL. This subset of TCF1+ exhausted T cells correlates with good clinical response to immune checkpoint therapy and may improve prediction of anti-PD-1 response in patients with THRLBCL.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Antígeno B7-H1 Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Blood Adv Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Antígeno B7-H1 Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Blood Adv Ano de publicação: 2022 Tipo de documento: Article