Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Foxp3 and CD68 as Potential Predictors of Response to Immune Checkpoint Inhibitors in Patients with Advanced Solid Tumor

Peter Grell
* ORCID logo ,
Simona Borilova
ORCID logo ,
Pavel Fabian
,
Iveta Selingerova
ORCID logo ,
David Novak
,
Petr Muller
ORCID logo ,
Igor Kiss
,
Rostislav Vyzula
Version 1 : Received: 15 January 2023 / Approved: 18 January 2023 / Online: 18 January 2023 (08:39:18 CET)

A peer-reviewed article of this Preprint also exists.

Grell, P.; Borilova, S.; Fabian, P.; Selingerova, I.; Novak, D.; Muller, P.; Kiss, I.; Vyzula, R. 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 2023, 15, 1901. Grell, P.; Borilova, S.; Fabian, P.; Selingerova, I.; Novak, D.; Muller, P.; Kiss, I.; Vyzula, R. 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 2023, 15, 1901.

Abstract

Immune checkpoint inhibitors (ICI) are currently use in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. Aim of our study was to find predictive biomarkers of ICI treatment. We analyzed by immunohistochemistry various cell subsets, including CD3+ cells, CD8+ cells, CD68+ cells, CD20+ cells, FoxP3+ cells, and molecules as LAG-3, IDO1, TGfβ. Comprehensive genomic profiles were analyzed. Correlation of various biomarkers with efficacy of ICI treatment in patients with advanced solid tumors was evaluated. We evaluated 56 patients treated with ICI monotherapy. Longer median progression-free survival (PFS) was found in tumors negative for nuclear FoxP3 (P = 0.002, HR 0.14) and in TMB-high tumors (P = 0.024, HR 0.38). Longer overall survival (OS) was found in patient with intraepithelial CD8 negativity (P = 0.045, HR 0.47). In malignant melanoma CD68 negativity, FoxP3 negativity and PDL TPS ≥ 1 was associated with longer PFS. In NSCLC FoxP3 was associated with longer PFS and OS. We found that absence of expression of several biomarkers such as CD68 and FoxP3 is associated with better survival. TMB-high and PD-L1 expression not universally but in certain disease could predict response.

Keywords

Immune checkpoint inhibitors; Anti-tumor immunity; Predictive biomarker; Malignant melanoma; NSCLC

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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