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Contemporary Practices in Immunotherapy-Guided Management of Lung Cancer

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A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 July 2026) | Viewed by 3411

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Editors

Dr. Eleni Karapanagiotou

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Guest Editor

Department of Thoracic Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Interests: non-small cell lung carcinoma; immunotherapy

Dr. Nikolaos Syrigos

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Guest Editor

Department of Oncology, Guy’s and St. Thomas Hospitals NHS Foundation Trust, London, UK
Interests: non-small cell lung carcinoma; immunotherapy

Umair Mahmood

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Guest Editor Assistant

Department of Oncology, Guy’s and St. Thomas Hospitals NHS Foundation Trust, London, UK
Interests: non-small cell lung carcinoma; precision medicine; immunotherapy; clinical bioinformatics

Special Issue Information

Dear Colleagues,

This Special Issue will assemble current evidence and emerging insights on contemporary practices in immunotherapy-guided management of lung cancer. As ICIs are now embedded across perioperative, locally advanced, and metastatic treatment pathways, clinicians are encountering certain practical questions in daily practice. These include identifying which patients are most likely to benefit, recognizing and managing toxicities at an early stage, and determining how best to modify treatment when resistance arises.

We are pleased to invite the submission of studies examining innovative clinical strategies, biomarkers refining patient selection, and evolving paradigms that integrate ICIs into multimodal care. This Special Issue will highlight advances that are shaping personalized, immunologically informed lung cancer treatment in modern clinical practice.

For this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

Strategies for managing oligoprogression on ICIs with integrated radiotherapy;
Evaluating outcomes and optimizing management of ICI-related toxicities;
Biomarker-driven patient stratification for immunotherapy;
AI-enabled prediction of immunotherapy response and long-term outcomes in younger patients with lung cancer;
Approaches to resistance mechanisms and adaptation of ICI-based regimens.

We look forward to receiving your contributions.

Dr. Eleni Karapanagiotou
Dr. Nikolaos Syrigos
Guest Editors

Umair Mahmood
Guest Editor Assistant

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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers 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 2900 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
immunotherapy
oligoprogressive disease
radiotherapy
artificial intelligence

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Published Papers (3 papers)

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Research

21 pages, 2468 KB

Open AccessArticle

Peripheral CD8+ T Cell Dynamics and Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Following Bronchoscopic Cryotherapy and Pembrolizumab-Based Therapy

by Gediminas Vasiliauskas, Evelina Žemaitė, Erika Skrodenienė, Lina Poškienė, Skaidrius Miliauskas and Marius Žemaitis

Cancers 2026, 18(11), 1793; https://doi.org/10.3390/cancers18111793 - 31 May 2026

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Abstract

Background: Bronchoscopic cryotherapy may enhance anti-tumor immunity and improve the effect of immune checkpoint blockade, but CD8+ T cell dynamics after cryotherapy combined with pembrolizumab-based therapy in metastatic non-small cell lung cancer (NSCLC) remain insufficiently characterized. Methods: In this prospective, exploratory, randomized, controlled, single-center study, metastatic NSCLC patients were assigned to bronchoscopic cryotherapy performed 7 ± 1 days before first-line pembrolizumab-based therapy or to standard treatment alone. Peripheral blood mononuclear cells were analyzed by flow cytometry at baseline, week 3, and week 6. CD8+ T cell subsets defined by CD45RO, CD28, granzyme B (GzB), IFNγ, Ki-67, and PD-1 were evaluated in relation to treatment group, radiologic response, progression-free survival (PFS), and overall survival (OS). Results: Flow cytometry was performed in 76 patients, including 34 in the cryotherapy group and 42 in the control group. Cryotherapy was associated with a treatment-specific increase in circulating GzB+ CD8+ T cells by week 6. In contrast, Ki-67+ CD8+ and GzB+Ki-67+ cells increased in both treatment groups, suggesting that early peripheral CD8+ proliferation was largely shared across pembrolizumab-based therapy. Radiologic responders demonstrated more sustained proliferative CD8+ dynamics, most consistently reflected by increased CD28+ Ki-67+ cells. In exploratory landmark survival analyses, a higher week-3-to-baseline GzB+ Ki-67+ CD8+ ratio showed a hypothesis-generating association with longer PFS and OS. Conclusions: In metastatic NSCLC patients receiving first-line pembrolizumab-based therapy, the addition of bronchoscopic cryotherapy was associated with peripheral CD8+ T cell remodeling toward enhanced cytotoxic activity. Proliferative CD8+ T cell changes were associated with radiologic response and better survival. These findings support bronchoscopic cryotherapy as a potential immune-modulating adjunct and warrant validation in larger studies. Full article

(This article belongs to the Special Issue Contemporary Practices in Immunotherapy-Guided Management of Lung Cancer)

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15 pages, 587 KB

Open AccessArticle

Impact of Immune-Related Adverse Event Frequency, Severity and Corticosteroid Use on Immune Checkpoint Inhibitor Efficacy in Non-Small Cell Lung Cancer

by José del Corral-Morales, Carlos Ayala-de Miguel, Laura Quintana-Cortés, Santiago González-Santiago, José Fuentes-Pradera and Pablo Ayala-de Miguel

Cancers 2026, 18(10), 1538; https://doi.org/10.3390/cancers18101538 - 9 May 2026

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Abstract

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of non-small cell lung cancer (NSCLC), introducing a distinct spectrum of immune-related toxicities (irAEs). However, the real-world impact of irAEs and corticosteroid use on treatment outcomes remains uncertain. Methods: We conducted a multicenter, retrospective study including patients with advanced NSCLC treated with ICIs alone or in combination with chemotherapy between April 2017 and December 2023. Clinical records were reviewed to collect data on irAEs and corticosteroid administration. Efficacy and safety outcomes were compared according to irAE occurrence, grade, and corticosteroid use. Categorical variables were analyzed using chi-square tests, while PFS and OS were estimated using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards models were used to estimate HRs and 95% CIs. Results: Among 452 patients, 151 (33.4%) experienced irAEs of any grade, and 37 (8.2%) developed grade ≥3 events. The most common irAEs were dermatologic (11.1%), endocrine disorders (9.1%), and arthritis (5.5%). Corticosteroids were administered for irAE management in 60 patients (13.3%). Patients who developed irAEs achieved significantly improved progression-free survival (median PFS: 23.2 vs. 4.2 months; HR = 0.29; p < 0.001) and overall survival (median OS: 31.2 vs. 7.6 months; HR = 0.35; p < 0.001), including those with grade ≥3 events. The survival benefit associated with irAEs was not compromised by corticosteroid (CS) use for irAE management (median PFS 46.3 in irAE vs. 5.5 months in non-irAE/no use; HR = 0.28; p < 0.001). Temporary ICI discontinuation due to irAEs was associated with longer median PFS (39.1 vs. 5.6 months; HR = 0.29; p < 0.001), as was permanent ICI discontinuation due to irAEs (median not reached vs. 7.4 months; HR = 0.20; p < 0.001). Conclusions: In this retrospective cohort, the occurrence of irAEs—and their management with CS—was associated with enhanced ICI efficacy in metastatic NSCLC, including among patients who developed high-grade toxicities and those who discontinued treatment due to toxicity. Full article

(This article belongs to the Special Issue Contemporary Practices in Immunotherapy-Guided Management of Lung Cancer)

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17 pages, 1380 KB

Open AccessArticle

Outcomes Following Radiotherapy for Oligoprogressive NSCLC on Immune Checkpoint Inhibitors: A Real-World, Multinational Experience

by Umair Mahmood, Eleni Josephides, Nicholas Coupe, Daniel Smith, Shahreen Ahmad, Omar Al-Salihi, Sze M. Mak, Meenali Chitnis, Alexandros Georgiou, Daniel Ajzensztejn, Eleni Karapanagiotou, Geoff S. Higgins, Niki Panakis, Jonathan D. Schoenfeld and Michael Skwarski

Cancers 2026, 18(1), 71; https://doi.org/10.3390/cancers18010071 - 25 Dec 2025

Cited by 1 | Viewed by 1500

Abstract

Purpose: We conducted the largest multinational review to date evaluating outcomes following radiotherapy for non-small cell lung carcinoma (NSCLC) patients with oligoprogressive disease (OPD) on immune checkpoint inhibitors (ICIs). Methods: Patients with NSCLC irradiated to ≤5 progressive lesions while receiving ICIs between 2010 and 2023 were identified. We evaluated predictors of local control (LC), progression-free survival (PFS), and overall survival (OS). Patient demographics, disease characteristics, and survival were analyzed using the Wilcoxon test, Kaplan-Meier methods, and uni-/multivariate Cox models. Results: Out of 1178 treated patients, 103 eligible ones were included. The median OPD lesion was 1; the most common site was the lung (n = 33). The median LC of irradiated OPD lesions was not reached. Median PFS and OS were 6.90 (5.75–12.91) and 23.46 (17.54–37.16) months, respectively. Patient demographics, tumor pathological factors, number of OPD lesions, cumulative tumor volume, radiation modality, and OPD response to prior ICIs before radiation were not associated with these three outcomes. However, LC was associated with intermediate/high radiation doses (p = 0.005) and local response to radiation (p = 0.007). Improved PFS was associated with visceral OPD sites following radiation (p = 0.01). A favorable OS was associated with intermediate/high radiation doses (p = 0.01), local response to radiation (p = 0.006), and duration of last ICI before OPD (p = 0.03). Conclusions: Promising outcomes were observed with ICI and radiation for visceral OPD at intermediate/high doses. Prolonged ICI use before OPD and local response to radiotherapy improved survival. These data can contribute towards guidance of multidisciplinary clinical decision-making for managing OPD in NSCLC patients receiving ICIs. Full article

(This article belongs to the Special Issue Contemporary Practices in Immunotherapy-Guided Management of Lung Cancer)

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