Integration of peripheral blood- and tissue-based biomarkers of response to immune checkpoint blockade in urothelial carcinoma.

Autor: Vanguri RS; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Smithy JW; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Li Y; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Zhuang M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Maher CA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Aleynick N; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Peng X; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Al-Ahmadie H; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Funt SA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Rosenberg JE; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Iyer G; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Bajorin D; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Mathews JC; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Nadeem S; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Panageas KS; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Shen R; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Callahan MK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Hollmann TJ; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.; Bristol Myers Squibb, Princeton, NJ, USA.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2023 Nov; Vol. 261 (3), pp. 349-360. Date of Electronic Publication: 2023 Sep 05.
DOI: 10.1002/path.6197
Abstrakt: As predictive biomarkers of response to immune checkpoint inhibitors (ICIs) remain a major unmet clinical need in patients with urothelial carcinoma (UC), we sought to identify tissue-based immune biomarkers of clinical benefit to ICIs using multiplex immunofluorescence and to integrate these findings with previously identified peripheral blood biomarkers of response. Fifty-five pretreatment and 12 paired on-treatment UC specimens were identified from patients treated with nivolumab with or without ipilimumab. Whole tissue sections were stained with a 12-plex mIF panel, including CD8, PD-1/CD279, PD-L1/CD274, CD68, CD3, CD4, FoxP3, TCF1/7, Ki67, LAG-3, MHC-II/HLA-DR, and pancytokeratin+SOX10 to identify over three million cells. Immune tissue densities were compared to progression-free survival (PFS) and best overall response (BOR) by RECIST version 1.1. Correlation coefficients were calculated between tissue-based and circulating immune populations. The frequency of intratumoral CD3 + LAG-3 + cells was higher in responders compared to nonresponders (p = 0.0001). LAG-3 + cellular aggregates were associated with response, including CD3 + LAG-3 + in proximity to CD3 + (p = 0.01). Exploratory multivariate modeling showed an association between intratumoral CD3 + LAG-3 + cells and improved PFS independent of prognostic clinical factors (log HR -7.0; 95% confidence interval [CI] -12.7 to -1.4), as well as established biomarkers predictive of ICI response (log HR -5.0; 95% CI -9.8 to -0.2). Intratumoral LAG-3 + immune cell populations warrant further study as a predictive biomarker of clinical benefit to ICIs. Differences in LAG-3 + lymphocyte populations across the intratumoral and peripheral compartments may provide complementary information that could inform the future development of multimodal composite biomarkers of ICI response. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
(© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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