FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer

Immune checkpoint inhibitors (ICI) are the main therapy currently used in advanced malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Despite the wide variety of uses, the possibility of predicting ICI efficacy in these tumor types is scarce. The aim of our study was to find new predict...

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Main Authors: Peter Grell, Simona Borilova, Pavel Fabian, Iveta Selingerova, David Novak, Petr Muller, Igor Kiss, Rostislav Vyzula
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/6/1901
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author Peter Grell
Simona Borilova
Pavel Fabian
Iveta Selingerova
David Novak
Petr Muller
Igor Kiss
Rostislav Vyzula
author_facet Peter Grell
Simona Borilova
Pavel Fabian
Iveta Selingerova
David Novak
Petr Muller
Igor Kiss
Rostislav Vyzula
author_sort Peter Grell
collection DOAJ
description Immune checkpoint inhibitors (ICI) are the main therapy currently used in advanced malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Despite the wide variety of uses, the possibility of predicting ICI efficacy in these tumor types is scarce. The aim of our study was to find new predictive biomarkers for ICI treatment. We analyzed, by immunohistochemistry, various cell subsets, including CD3+, CD8+, CD68+, CD20+, and FoxP3+ cells, and molecules such as LAG-3, IDO1, and TGFβ. Comprehensive genomic profiles were analyzed. We evaluated 46 patients with advanced MM (31) and NSCLC (15) treated with ICI monotherapy. When analyzing the malignant melanoma group, shorter median progression-free survival (PFS) was found in tumors positive for nuclear FoxP3 in tumor-infiltrating lymphocytes (TILs) (<i>p</i> = 0.048, HR 3.04) and for CD68 expression (<i>p</i> = 0.034, HR 3.2). Longer PFS was achieved in patients with tumors with PD-L1 TPS ≥ 1 (<i>p</i> = 0.005, HR 0.26). In the NSCLC group, only FoxP3 positivity was associated with shorter PFS and OS. We found that FoxP3 negativity was linked with a better response to ICI in both histological groups.
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spelling doaj.art-7ad2cc638e0f4d0d8dca32f6bb338aa42023-11-17T10:08:47ZengMDPI AGCancers2072-66942023-03-01156190110.3390/cancers15061901FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung CancerPeter Grell0Simona Borilova1Pavel Fabian2Iveta Selingerova3David Novak4Petr Muller5Igor Kiss6Rostislav Vyzula7Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicDepartment of Pathology, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicResearch Center for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicResearch Center for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicResearch Center for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicDepartment of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech RepublicImmune checkpoint inhibitors (ICI) are the main therapy currently used in advanced malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Despite the wide variety of uses, the possibility of predicting ICI efficacy in these tumor types is scarce. The aim of our study was to find new predictive biomarkers for ICI treatment. We analyzed, by immunohistochemistry, various cell subsets, including CD3+, CD8+, CD68+, CD20+, and FoxP3+ cells, and molecules such as LAG-3, IDO1, and TGFβ. Comprehensive genomic profiles were analyzed. We evaluated 46 patients with advanced MM (31) and NSCLC (15) treated with ICI monotherapy. When analyzing the malignant melanoma group, shorter median progression-free survival (PFS) was found in tumors positive for nuclear FoxP3 in tumor-infiltrating lymphocytes (TILs) (<i>p</i> = 0.048, HR 3.04) and for CD68 expression (<i>p</i> = 0.034, HR 3.2). Longer PFS was achieved in patients with tumors with PD-L1 TPS ≥ 1 (<i>p</i> = 0.005, HR 0.26). In the NSCLC group, only FoxP3 positivity was associated with shorter PFS and OS. We found that FoxP3 negativity was linked with a better response to ICI in both histological groups.https://www.mdpi.com/2072-6694/15/6/1901immune checkpoint inhibitorsanti-tumor immunitypredictive biomarkermalignant melanomaNSCLC
spellingShingle Peter Grell
Simona Borilova
Pavel Fabian
Iveta Selingerova
David Novak
Petr Muller
Igor Kiss
Rostislav Vyzula
FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer
Cancers
immune checkpoint inhibitors
anti-tumor immunity
predictive biomarker
malignant melanoma
NSCLC
title FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer
title_full FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer
title_fullStr FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer
title_full_unstemmed FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer
title_short FoxP3 Expression in Tumor-Infiltrating Lymphocytes as Potential Predictor of Response to Immune Checkpoint Inhibitors in Patients with Advanced Melanoma and Non-Small Cell Lung Cancer
title_sort foxp3 expression in tumor infiltrating lymphocytes as potential predictor of response to immune checkpoint inhibitors in patients with advanced melanoma and non small cell lung cancer
topic immune checkpoint inhibitors
anti-tumor immunity
predictive biomarker
malignant melanoma
NSCLC
url https://www.mdpi.com/2072-6694/15/6/1901
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