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Predictive Biomarkers and Immunotherapy Strategies for Non-small Cell Lung Cancer

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 9859

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Special Issue Editor

Dr. Eva Maria Garrido-Martín

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Guest Editor

Cell Biology Department, Research and Development, Oncology Business Unit. PharmaMar, Madrid, Spain
Interests: cancer; drug discovery; biomarkers; preclinical models

Special Issue Information

Dear Colleagues,

Immunotherapy has revolutionized the landscape of lung cancer treatment in recent years. New immunotherapy strategies have positively affected patient survival, especially in non-small cell lung cancer. While immunotherapy is achieving amazing results, especially with the development of therapies that recognize and block immune checkpoints such as PD-1/PD-L1 axis and CTLA4, great efforts are still ongoing in the search for predictive biomarkers that allow patient selection in the context of personalized medicine. In addition to the high cost of immunotherapies, the reason underlying this incessant search for novel biomarkers lies essentially in the relevant side effects that these therapies can eventually produce. Patient selection would be essential in order to avoid treatment to candidates in which certain biomarkers will predictably provide poor or null therapeutic benefit. Despite recent efforts made in the field, focused on the expression of certain immune checkpoints, lymphocyte infiltration and tumor mutational burden, to date, there is only one approved marker for use in clinic, which is the expression of PD-L1 by the tumor tissue. This biomarker is far from optimal, due to several technical aspects and tumoral heterogeneity. The aim of this Special Issue is to highlight the most recent advances in the context of new available immunotherapies and in the prediction of response to immunotherapies with the development of novel robust and multiparametric biomarkers.

Dr. Eva Maria Garrido-Martín
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Lung cancer
Biomarkers
Immunotherapies
Immune checkpoints
TMB
PD-L1

Published Papers (3 papers)

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Research

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20 pages, 3042 KiB

Open AccessArticle

Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy

by Javier Ramos-Paradas, David Gómez-Sánchez, Aranzazu Rosado, Alvaro C. Ucero, Irene Ferrer, Ricardo García-Luján, Jon Zugazagoitia, Nuria Carrizo, Ana B. Enguita, Esther Conde, Eva M. Garrido-Martin and Luis Paz-Ares

J. Clin. Med. 2022, 11(6), 1500; https://doi.org/10.3390/jcm11061500 - 9 Mar 2022

Cited by 3 | Viewed by 3698

Abstract

Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors has shown outstanding results in NSCLC, the precise identification of responders remains a major challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined. We hypothesized that specific molecular aberrations may impact the immune microenvironment in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify robust predictive biomarkers and improve potential benefits from immunotherapy. We established a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features were comprehensively characterized by genomic and immune-targeted sequencing panels along with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed higher immune infiltration and upregulated genes involved in potentiating immune responses when compared to pro-tumorigenic samples, which favored tumoral progression. This classification identified a set of biomarkers that could potentially predict response to immunotherapy. These results could improve patient selection and expand potential benefits from immunotherapy. Full article

(This article belongs to the Special Issue Predictive Biomarkers and Immunotherapy Strategies for Non-small Cell Lung Cancer)

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14 pages, 1401 KiB

Open AccessArticle

The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab

by Edoardo Lenci, Luca Cantini, Federica Pecci, Valeria Cognigni, Veronica Agostinelli, Giulia Mentrasti, Alessio Lupi, Nicoletta Ranallo, Francesco Paoloni, Silvia Rinaldi, Linda Nicolardi, Andrea Caglio, Sophie Aerts, Alessio Cortellini, Corrado Ficorella, Rita Chiari, Massimo Di Maio, Anne-Marie C. Dingemans, Joachim G. J. V. Aerts and Rossana Berardi

J. Clin. Med. 2021, 10(5), 1005; https://doi.org/10.3390/jcm10051005 - 2 Mar 2021

Cited by 27 | Viewed by 2950

Abstract

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 − GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting. Full article

(This article belongs to the Special Issue Predictive Biomarkers and Immunotherapy Strategies for Non-small Cell Lung Cancer)

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Review

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16 pages, 1323 KiB

Open AccessReview

Blood Biomarkers of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

by Yolanda Lage Alfranca, María Eugenia Olmedo Garcia, Ana Gómez Rueda, Pablo Álvarez Ballesteros, Diana Rosero Rodríguez and Marisa Torres Velasco

J. Clin. Med. 2022, 11(11), 3245; https://doi.org/10.3390/jcm11113245 - 6 Jun 2022

Cited by 7 | Viewed by 2457

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), either used in monotherapy or in combination with chemotherapy. While some patients achieve durable responses, some will not get benefit from this treatment. Early identification of non- responder patients could avoid unnecessary treatment, potentially serious immune-related adverse events and reduce treatment costs. PD-L1 expression using immunohistochemistry is the only approved biomarker for the selection of patients that can benefit from immunotherapy. However, application of PD-L1 as a biomarker of treatment efficacy shows many deficiencies probably due to the complexity of the tumor microenvironment and the technical limitations of the samples. Thus, there is an urgent need to find other biomarkers, ideally blood biomarkers to help us to identify different subgroups of patients in a minimal invasive way. In this review, we summarize the emerging blood-based markers that could help to predict the response to ICIs in NSCLC. Full article

(This article belongs to the Special Issue Predictive Biomarkers and Immunotherapy Strategies for Non-small Cell Lung Cancer)

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