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Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma

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Abstract

Background

Melanoma-associated antigen-A (MAGE-A) and programmed-death ligand 1 (PD-L1) are present in urothelial carcinoma (UC). We assessed survival outcomes in patients with MAGE-A and PD-L1 expression.

Methods

MAGE-A and PD-L1 expression on neoplastic cells was analyzed using tissue microarrays from patients with UC. We compared differential expression between disease stage and grade. MAGE-A and PD-L1 co-expression was subcategorized. Fisher’s exact test was done for categorical variables followed by univariable and multivariable analysis of recurrence-free survival (RFS) and progression-free survival (PFS).

Results

Co-expression of MAGE+/PD-L1+ was higher in advanced disease; however, only MAGE+/PD-L1− was associated with shorter RFS [hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.19–2.99; p = .006]. MAGE+/PD-L1+ was associated with the worst PFS (HR 17.1; 95% CI 5.96–49.4; p ≤ .001). MAGE-A expression was more prevalent with high-grade (p = .015), and higher-stage ≥ pT2 (p = .001) disease. The 5-year RFS was 44% for MAGE+ versus 58% for MAGE− patients. On multivariable analysis, MAGE+ was also associated with shorter RFS (HR 1.55; 95% CI 1.05–2.30; p = .03). Similarly, MAGE+ was associated with shorter PFS (HR 3.12; 95% CI 1.12–8.68; p = .03).

Conclusion

MAGE-A and PD-L1 expression is increased in advanced disease and associated with shorter PFS. Furthermore, MAGE-A expression was significantly associated with higher-grade and -stage disease and associated with shorter RFS and PFS. The worse prognosis associated with MAGE-A+/PD-L1+ provides evidence that a combinatorial treatment strategy co-targeting MAGE/PD-L1 might be feasible. Further studies are needed to validate these findings.

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Abbreviations

CI:

Confidence interval

HR:

Hazard ratio

IQR:

Inter-quartile range

MAGE-A:

Melanoma-associated antigen-A

MP:

MAGE-positive

MN:

MAGE-negative

PD-L1:

Programmed death-ligand 1

RC:

Radical cystectomy

RFS:

Recurrence-free survival

TCR:

Adoptive T-cell receptor-engineered T-cell therapy

TMA:

Tissue microarray

UC:

Urothelial carcinoma

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Funding

Research funding was provided by Kite, a Gilead Company. Biomedical editing was sponsored by Kite, a Gilead Company.

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Authors and Affiliations

  1. Department of Urology, Institute of Urologic Oncology, David Geffen School of Medicine at University of California, 300 Stein Plaza, Suite 348, Los Angeles, CA, 90095, USA

    Izak Faiena, Karim Chamie, Arie S. Belldegrun, Allan J. Pantuck & Alexandra Drakaki

  2. Kite, A Gilead Company, Santa Monica, CA, USA

    Stephanie H. Astrow, Rajul Jain & Adrian Bot

  3. Department of Medicine Statistics Core, David Geffen School of Medicine at University of California, Los Angeles, CA, USA

    David A. Elashoff

  4. Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, USA

    Alexandra Drakaki

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  1. Izak Faiena
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Contributions

IF: Conception, data collection, data analysis, drafting manuscript, critical revisions. SHA: Conception, drafting manuscript, critical revisions. DAE: Data analysis, drafting manuscript, critical revisions. RJ: Drafting manuscript, critical revisions. AB: Conception, drafting manuscript, critical revisions. KC: Conception, drafting manuscript, critical revisions. ASB MD: Conception, critical revisions. AJP: Conception, drafting manuscript, critical revisions. AD: Conception, drafting manuscript, critical revisions.

Corresponding author

Correspondence to Izak Faiena.

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Conflict of interest

Izak Faiena and Alexandra Drakaki received research funding from Kite, a Gilead Company. Stephanie H. Astrow, Rajul Jain, and Adrian Bot are employees of Kite, a Gilead Company, and have equity ownership in Gilead Sciences, Inc. Arie S. Belldegrun is the founder and was formerly Chief Executive Officer of Kite, a Gilead Company, and has equity ownership in Gilead Sciences, Inc. Allan J. Pantuck has equity ownership in Gilead Sciences, Inc. The authors declare they have no other conflicts of interest.

Ethical approval and ethical standards

This study included de-identified data in a tissue microarray and was deemed to be an exempt study by the institutional review board (IRB #99–233) of the University of California, Los Angeles for TMA construction and data analysis; therefore, special ethical permission was not required. Requirement for consent was waived given the retrospective, de-identified nature of the samples, and the impracticality of consenting for samples stored prior to 1998.

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Faiena, I., Astrow, S.H., Elashoff, D.A. et al. Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma. Cancer Immunol Immunother 68, 743–751 (2019). https://doi.org/10.1007/s00262-019-02316-w

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