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Cancer testis antigens in myelodysplastic syndromes revisited: a targeted RNA-seq approach

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Lopez, AMH
  • Chen-Liang TH
  • Zurdo M
  • Carrillo-Tornel S
  • Salido EJ
  • Beltrán V
  • Muina, Begona
  • Amigo M
  • Navarro-Villamor N
  • Cifuentes R
  • Antón AI
  • Teruel R
  • Muro M
  • Vicente V
  • Jerez A

Abstract

Cancer-Testis antigens (CTA) are named after the tissues where they are mainly expressed: in germinal and in cancer cells, a process that mimics many gametogenesis features. Mapping accurately the CTA gene expression signature in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) is a prerequisite for downstream immune target-discovery projects. In this study, we take advantage of the use of azacitidine to treat high-risk MDS and CMML to draw the CTAs landscape, before and after treatment, using anad hoctargeted RNA sequencing (RNA-seq) design for this group of low transcript genes. In 19 patients, 196 CTAs were detected at baseline. Azacitidine did not change the number of CTAs expressed, but it significantly increased or decreased expression in nine and five CTAs, respectively.TFDP3andDDX53, emerged as the main candidates for immunotherapeutic targeting, as they showed three main features: i) a significant derepression on day +28 of cycle one in those patients who achieved complete remission with hypomethylating treatment (FC = 6,p= .008; FC = 2.1,p= .008, respectively), ii) similar dynamics at the protein level to what was observed at the RNA layer, and iii) to elicit significant specific cytotoxic immune responses detected by TFDP3 and DDX53 HLA-A*0201 tetramers. Our study addresses the unmet landscape of CTAs expression in MDS and CMML and revealed a previously unrecognizedTFDP3andDDX53reactivation, detectable in plasma and able to elicit a specific immune response after one cycle of azacitidine.

Datos de la publicación

ISSN/ISSNe:
2162-402X, 2162-4011

OncoImmunology  Landes Bioscience

Tipo:
Article
Páginas:
1824642-1824642
PubMed:
33101773
Factor de Impacto:
3,049 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 4

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Keywords

  • Cancer testis antigens; azacitidine; myelodysplastic syndromes; t-cell response

Proyectos y Estudios Clínicos

CARACTERIZACIÓN EPIGENÓMICA DE LA ANOREXIA NERVIOSA. MODELO DE GEMELAS MONOCIGOTAS DISCORDANTES Y VALIDACIÓN EN POBLACIÓN GENERAL.

Investigador Principal: LUIS MIGUEL ROJO MORENO

PI16/01279 . INSTITUTO DE SALUD CARLOS III . 2017

RASTREO Y VALIDACION DE MUTACIONES EN REGIONES NO CODIFICANTES Y EN GENES DEL SPLICEOSOMA EN LA LEUCEMIA MIELOBLÁSTICA AGUDA (LMA).

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

PI16/01113 . INSTITUTO DE SALUD CARLOS III . 2017

MEDICINA DE PRECISIÓN EN RECAÍDAS DE CÁNCER PEDIÁTRICO NEUROBLÁSTICO MEDIANTE SECUENCIACION MASIVA DE NUEVA GENERACIÓN (NGS).

Investigador Principal: INÉS CALABRIA TORRES

GV/2017/135 . CONSELLERIA DE EDUCACION . 2017

Identificación temprana de nuevas alteraciones genéticas pronósticas y accionables en biopsia líquida de pacientes pediátricos con tumores sólidos.

Investigador Principal: SANDRA DOLZ GIMÉNEZ

PI18/00521 . INSTITUTO DE SALUD CARLOS III . 2019

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