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. 2022 Jun 12;14(12):2898.
doi: 10.3390/cancers14122898.

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC

Jacobo Rogado  1   2 , Fernando Pozo  3 , Kevin Troule  3 , José Miguel Sánchez-Torres  2   4 , Nuria Romero-Laorden  2   4 , Rebeca Mondejar  2   4   5 , Olga Donnay  2   4 , Anabel Ballesteros  2   4 , Vilma Pacheco-Barcia  2   6 , Javier Aspa  2   7 , Fátima Al-Shahrour  3 , Arantzazu Alfranca  2   8 , Ramon Colomer  2   4   5
Affiliations

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC

Jacobo Rogado et al. Cancers (Basel). .

Abstract

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each biomarker, defined as those above the 55th or below the 45th percentile of the overall marker expression within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patients.

Keywords: anti-PD-1 antibodies; biomarkers; immunotherapy; non-small cell lung cancer; peripheral blood mononuclear cells.

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Conflict of interest statement

Jacobo Rogado reports personal fees from Roche, AstraZeneca, Merck, Ferrer, Persan Farma, Fresenius Kabi; travel expenses from MSD, BMS, Roche, and AstraZeneca; and advisor consultancies from Fresenius Kabi. Nuria Romero reports advisory consultancies from Ipsen, Janssen, Clovis, and Astra Zeneca and research funding from Janssen, MSD, and Pfizer. Ramon Colomer reports research funding from Roche, Janssen, BMS, and MSD. All of the declared conflicts of interest are outside of the submitted work. All other authors have no conflict to declare.

Figures

Figure 1
Figure 1
Overall survival Kaplan–Meier curves showing overall survival differences between immunotherapy treatment (IT) study group versus control group. The Kaplan–Meier curves show the differences in survival according the high or low expression of each peripheral blood mononuclear cell subpopulation studied in both groups. In addition, the log-rank test, multivariate cox regression models, and the median overall survival values with their range are reflected. Graphics (a,b) show overall survival in immunotherapy treatment group (a) versus study group (b) according to the expression of T-helper lymphocytes CCR9+. Graphics (c,d) show overall survival in immunotherapy treatment group (c) versus study group (d) according to the expression of T-helper lymphocytes CCR10+. Graphics (e,f) show overall survival in immunotherapy treatment group (e) versus study group (f) according to the expression of T-cytotoxic lymphocytes CXCR4+.
Figure 2
Figure 2
Overall survival and progression-free survival Kaplan–Meier curves showing overall survival differences in study group according to T-helper lymphocytes expressing CCR9 baseline levels in non-responder patients. The Kaplan–Meier curves show the differences in survival according the high or low expression of T-helper lymphocytes expressing CCR9 in the study group. In addition, the log-rank test, multivariate cox regression models, and the median of overall/progression-free survival and their range values are reflected.
Figure 3
Figure 3
Overall survival and progression-free survival Kaplan–Meier curves in study and control groups according to the best immune biomarkers detected. The Kaplan-Meier curves show the differences in survival according the high or low expression of each peripheral blood mononuclear cell subpopulation studied in immunotherapy treated (IT) group and in control group treated with non-immunotherapy drugs. In addition, the log-rank test, multivariate cox regression models, and the median progression-free and overall survival values with their range are reflected.
See this image and copyright information in PMC

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