Association of PD-1, LAG-3 and TIM-3 expression on intratumoral CD8 T-cells with response to atezolizumab in a Real-World-Evidence biomarker study for advanced urothelial carcinoma patients

Blockade of the PD-1/PD-L1 pathway is part of the standard treatment for advanced urothelial cancer, but reliable predictive biomarkers have not been identified. Here, we analyze with Multiplexed Quantitative Immunofluorescence the pretreatment tumor microenvironment (TME) of urothelial cancer samples from patients treated with atezolizumab to identify correlations with treatment efficacy in a Real-World-Evidence (RWE) study. We assessed with Multiplexed Quantitative Immunofluorescence the expression of CD8, PD-1, TIM-3 and LAG-3 on T-cells in the different compartments of the TME (tumor, stroma and whole tissue) in pre-treatment tissue microarrays. We studied associations between the expression of the markers and clinical efficacy. One hundred-nine patients received atezolizumab, showing an overall response rate of 23.8%. Safety was comparable to previous studies with atezolizumab. Pre-treatment tumor samples were available from 45 patients. CD8+ T-cell density was significantly increased in the tumor compartment, but not in the stromal compartment, of patients experiencing complete and partial responses, as compared with patients presenting stable disease or progression. Similar results were observed for co-expression of CD8/PD-1, CD8/TIM-3 and CD8/PD-1/TIM-3/LAG-3. Our findings support the relevance of the density and spatial distribution of CD8+ T-cells and its co-receptors for the clinical efficacy of single-agent PD-L1 blockade in patients with advanced urothelial cancer. RWE studies are a valuable tool for identifying predictive biomarkers.

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Journal
OncoImmunology
Published
2025-08-08
DOI
https://doi.org/10.1080/2162402x.2025.2538687
Citations
1
Primary Topic
Bladder and Urothelial Cancer Treatments
Type
article
Field-Weighted Citation Impact
2.01

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article

Association of PD-1, LAG-3 and TIM-3 expression on intratumoral CD8 T-cells with response to atezolizumab in a Real-World-Evidence biomarker study for advanced urothelial carcinoma patients

Eduardo Pujol, Marta Abengózar, Ignacio Méndez Ramírez, José Ángel Arranz et al.
1 citations
OncoImmunology
Bladder and Urothelial Cancer Treatments
2.01
article

Association of PD-1, LAG-3 and TIM-3 expression on intratumoral CD8 T-cells with response to atezolizumab in a Real-World-Evidence biomarker study for advanced urothelial carcinoma patients

Eduardo Pujol, Marta Abengózar, Ignacio Méndez Ramírez, José Ángel Arranz, Adriana Rosero, L. Mengíbar, Teresa Bonfill, Miguel F. Sanmamed, Ignacio Melero, Ángel Vizcay, Carlos E. de Andrea, José Luis Perez‐Gracia, Álvaro López‐Janeiro, Carmen Santander, Pablo Arnáiz, Javier Puente, J.M. Jurado, Carlos Álvarez Fernández, Eva Fernández, Miguel Ángel Climent, José Carlos Villa
article en
1 citations

Abstract

Blockade of the PD-1/PD-L1 pathway is part of the standard treatment for advanced urothelial cancer, but reliable predictive biomarkers have not been identified. Here, we analyze with Multiplexed Quantitative Immunofluorescence the pretreatment tumor microenvironment (TME) of urothelial cancer samples from patients treated with atezolizumab to identify correlations with treatment efficacy in a Real-World-Evidence (RWE) study. We assessed with Multiplexed Quantitative Immunofluorescence the expression of CD8, PD-1, TIM-3 and LAG-3 on T-cells in the different compartments of the TME (tumor, stroma and whole tissue) in pre-treatment tissue microarrays. We studied associations between the expression of the markers and clinical efficacy. One hundred-nine patients received atezolizumab, showing an overall response rate of 23.8%. Safety was comparable to previous studies with atezolizumab. Pre-treatment tumor samples were available from 45 patients. CD8+ T-cell density was significantly increased in the tumor compartment, but not in the stromal compartment, of patients experiencing complete and partial responses, as compared with patients presenting stable disease or progression. Similar results were observed for co-expression of CD8/PD-1, CD8/TIM-3 and CD8/PD-1/TIM-3/LAG-3. Our findings support the relevance of the density and spatial distribution of CD8+ T-cells and its co-receptors for the clinical efficacy of single-agent PD-L1 blockade in patients with advanced urothelial cancer. RWE studies are a valuable tool for identifying predictive biomarkers.

OncoImmunologyVol. 14(1)
Hospital General Universitario Gregorio Marañón (ES), Hospital Clínico San Carlos (ES), University of Oxford (GB), Hospital Virgen del Valle (ES), Fundación Instituto Valenciano de Oncología (ES), Navarre Institute of Health Research (ES), Instituto de Investigación Biosanitaria de Granada (ES), Hospital Universitario Miguel Servet (ES), Corporació Sanitària Parc Taulí (ES), Hospital General Universitario de Ciudad Real (ES), Hospital de Sabadell (ES), Institute of Immunology (HR), Hospital Universitario Central de Asturias (ES), Clinica Universidad de Navarra (ES), Hospital Clínico Universitario Lozano Blesa (ES), Onkologikoa (ES), Hospital Universitario de Valme (ES), Roche (Spain) (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Hospital Universitario Infanta Cristina (ES), Universidad de Navarra (ES)
Roche
Good health and well-being
Openalex Percentile: Top 13%
Bladder and Urothelial Cancer Treatments
2.01
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