Predictive and dynamic signature for anti-angiogenics in combination with PD-1 inhibitor in soft-tissue sarcoma: correlative studies linked to the IMMUNOSARC trial

IMMUNOSARC trial combined an anti-angiogenic agent (sunitinib) with a PD-1 inhibitor (nivolumab) in advanced sarcomas. Here we present the first correlative studies of the STS cohort enrolled in this trial.PURPOSEIMMUNOSARC trial combined an anti-angiogenic agent (sunitinib) with a PD-1 inhibitor (n...

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Published in:Clinical cancer research 2024-09
Main Authors: Moura, David S, Lopez-Marti, Jesus M, Benesova, Iva, de Andrea, Carlos, Di Lernia, Davide, Lacerenza, Serena, Mondaza-Hernandez, Jose L, Martin-Ruiz, Marta, Ramirez-Calvo, Marta, Grignani, Giovanni, Martinez-Trufero, Javier, Redondo, Andres, Valverde, Claudia, Stacchiotti, Silvia, Lopez-Pousa, Antonio, López-Guerrero, José A, Gutierrez, Antonio, Encinas-Tobajas, Victor, Hindi, Nadia, Sangiolo, Dario, Lopez-Martin, Jose A, Strizova, Zuzana Ozaniak, Martin-Broto, Javier
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Language:English
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Summary:IMMUNOSARC trial combined an anti-angiogenic agent (sunitinib) with a PD-1 inhibitor (nivolumab) in advanced sarcomas. Here we present the first correlative studies of the STS cohort enrolled in this trial.PURPOSEIMMUNOSARC trial combined an anti-angiogenic agent (sunitinib) with a PD-1 inhibitor (nivolumab) in advanced sarcomas. Here we present the first correlative studies of the STS cohort enrolled in this trial.Formalin-fixed paraffin-embedded (FFPE) and peripheral blood samples were collected at baseline and week 13. FFPE were used for transcriptomics and multiplex immunofluorescence, while peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients.EXPERIMENTAL DESIGNFormalin-fixed paraffin-embedded (FFPE) and peripheral blood samples were collected at baseline and week 13. FFPE were used for transcriptomics and multiplex immunofluorescence, while peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients.The density of intratumoral CD8+ T cells, measured by multiplexed immuno-phenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in gene expression of CD86, CHI3L1, CXCL10, CXCL9, LAG3, and VCAM1, and the decrease in the expression levels of NR4A1. In peripheral blood, 12 proteins were significantly modulated by treatment at W13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors separated two groups with distinct progression-free survival (PFS): 4.1 months (95% CI 3.5-NR) vs 17 months (95% CI 12.0 - NR), p=0.014. This molecular score was predictive of PFS when applied to the normalized data determined in the baseline samples.RESULTSThe density of intratumoral CD8+ T cells, measured by multiplexed immuno-phenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in gene expression of CD86, CHI3L1, CXCL10, CXCL9, LAG3, and VCAM1, and the decrease in the expression levels of NR4A1. In peripheral blood, 12 proteins were significantly modulated by treatment at W13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors
ISSN:1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-24-1782