| Autor: |
Vanguri, Rami S, Smithy, James W, Li, Yanyun, Zhuang, Mingqiang, Maher, Colleen A, Aleynick, Nathaniel, Peng, Xiyu, Al‐Ahmadie, Hikmat, Funt, Samuel A, Rosenberg, Jonathan E, Iyer, Gopa, Bajorin, Dean, Mathews, James C, Nadeem, Saad, Panageas, Katherine S, Shen, Ronglai, Callahan, Margaret K, Hollmann, Travis J |
| Předmět: |
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| Zdroj: |
Journal of Pathology; Nov2023, Vol. 261 Issue 3, p349-360, 12p |
| 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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