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. 2023 Apr 12:14:1158105.
doi: 10.3389/fimmu.2023.1158105. eCollection 2023.

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Yolanda Gonzalez-Montes  1 , Rocío Rodriguez-Romanos  1 , Alicia Villavicencio  1 , Gemma Osca-Gelis  1   2 , Marta González-Bártulos  1 , Francesca Llopis  1 , Victòria Clapes  3 , Albert Oriol  4 , Anna Sureda  3 , Lourdes Escoda  5 , Josep Sarrà  5 , Ana Garzó  1 , Natàlia Lloveras  1 , Isabel Díez  1 , Isabel Granada  4 , David Gallardo  1
Affiliations

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Yolanda Gonzalez-Montes et al. Front Immunol. .

Abstract

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.

Keywords: CTLA4 polymorphisms; bone marrow microenvironment; cytogenetics and molecular genetics; immune checkpoint; multiple myeloma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier curves of PFS according to CTLA4 rs2311775. (A) grouped phenotypes and (B) independent genotypes.
Figure 2
Figure 2
PFS for patients with ISS I-II according to CTLA4 rs2311775 genotype.
Figure 3
Figure 3
PFS for patients for patients receiving autologous stem cell transplant according to CTLA4 rs2311775 genotype.
See this image and copyright information in PMC

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Grants and funding

The study was supported by a grant from the Fundació Roses Contra el Cancer, Roses, Girona, Spain.