Ecto-calreticulin expression in multiple myeloma correlates with a failed anti-tumoral immune response and bad prognosis

Serrano Del Valle, Alfonso ; Beltrán-Visiedo, Manuel (Universidad de Zaragoza) ; de Poo-Rodríguez, Victoria ; Jiménez-Alduán, Nelia ; Azaceta, Gemma (Universidad de Zaragoza) ; Díez, Rosana (Universidad de Zaragoza) ; Martínez-Lázaro, Beatriz (Universidad de Zaragoza) ; Izquierdo, Isabel (Universidad de Zaragoza) ; Palomera, Luis (Universidad de Zaragoza) ; Naval, Javier (Universidad de Zaragoza) ; Anel, Alberto (Universidad de Zaragoza) ; Marzo, Isabel (Universidad de Zaragoza)

Resumen: Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38+ bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8+ T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells.

Idioma: Inglés

DOI: 10.1080/2162402X.2022.2141973

Año: 2022

Publicado en: OncoImmunology 11, 1 (2022), e2141973 [10 pp.]
ISSN: 2162-4011

Factor impacto JCR: 7.2 (2022)

Categ. JCR: ONCOLOGY rank: 47 / 241 = 0.195 (2022) - Q1 - T1
Categ. JCR: IMMUNOLOGY rank: 37 / 161 = 0.23 (2022) - Q1 - T1

Factor impacto CITESCORE: 12.5 - Immunology and Microbiology (Q1) - Medicine (Q1)

Factor impacto SCIMAGO: 2.003 - Immunology (Q1) - Oncology (Q1) - Immunology and Allergy (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B31-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011033
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2016-76338-R

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)