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Cancers
Special Issues
Immunotherapy in Non-Small Cell Lung Cancers
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Immunotherapy in Non-Small Cell Lung Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1753

Special Issue Editor

Dr. Marco Russano

E-Mail Website
Guest Editor
Department of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Álvaro del Portillo, 21, 00128 Rome, Italy
Interests: lung cancer; thoracic malignancies; immunotherapy; immune checkpoint inhibitors; targeted therapies

Special Issue Information

Dear Colleagues,

Within the last few years, immune checkpoint inhibitors (ICIs) have rapidly become the standard of care for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers. Recent evidence has led to their use even at the early stages as adjuvant and/or neoadjuvant treatment.

Certainly, immunotherapy has been shown to significantly improve patient survival compared with chemotherapy alone. However, there are still areas of unmet needs. Most patients develop resistance to treatment during the course of the disease, and only a minority of them have long-term benefits. PD-L1 expression is the only biomarker validated in clinical practice, but some limitations reduce its reliability, including mainly spatial and temporal heterogeneity. Several other biomarkers are under investigation, both tissue- and blood-derived, but need validation. Combination strategies (ICIs plus platinum-based chemotherapy) have emerged to increase response rates and survival, but not all patients respond or are eligible for chemotherapy.

This Special Issue aims to provide an overview of the current role of immunotherapy in NSCLC, but also gather new findings for future perspectives.

Dr. Marco Russano
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 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. 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

  • non-small cell lung cancer
  • immune checkpoint inhibitors
  • PD-1/PD-L1 blockade
  • immunotherapy
  • biomarkers

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Research

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11 pages, 1212 KiB  
Article
Comparison of PD-L1 Expression Between Preoperative Biopsy Specimens and Surgical Specimens in Non-Small Cell Lung Cancer
by Tadashi Sakaguchi, Akemi Iketani, Kentaro Ito, Yoichi Nishii, Koji Katsuta and Osamu Hataji
Cancers 2025, 17(3), 398; https://doi.org/10.3390/cancers17030398 - 25 Jan 2025
Viewed by 738
Abstract
Background: Recent advances in perioperative immunotherapies have led to a new era in the perioperative treatment of resectable, non-small cell lung cancer (NSCLC). Although the choice of neoadjuvant, adjuvant or perioperative immunotherapy remains controversial, few reports have compared programmed death ligand-1 (PD-L1) expression [...] Read more.
Background: Recent advances in perioperative immunotherapies have led to a new era in the perioperative treatment of resectable, non-small cell lung cancer (NSCLC). Although the choice of neoadjuvant, adjuvant or perioperative immunotherapy remains controversial, few reports have compared programmed death ligand-1 (PD-L1) expression as a biomarker between preoperative biopsy specimens and surgical specimens. Methods: We retrospectively reviewed consecutive patients with NSCLC whose preoperative biopsy specimens and surgical specimens were tested for PD-L1 (22C3) and PD-L1 (SP263), respectively, from June 2022 to February 2024. The three categorical classifications of PD-L1 expression (negative [<1%], low [1–49%], and high [≥50%]) were compared between the two tests. Results: Of the 33 patients, 13 patients had negative PD-L1 expression, 9 patients had low PD-L1 expression and 11 patients had high PD-L1 expression with preoperative biopsy specimens, while 18 patients had negative PD-L1 expression, 10 patients had low PD-L1 expression and 5 patients had high PD-L1 expression with surgical specimens. The concordance rate for the three categorical classifications of PD-L1 expression between the preoperative biopsy specimens and surgical specimens was 57.6%. Conclusions: PD-L1 expression may differ between preoperative biopsy specimens and surgical specimens. PD-L1 expression evaluated using small biopsy specimens may be largely influenced by chance due to intra-tumoral heterogeneity. Full article
(This article belongs to the Special Issue Immunotherapy in Non-Small Cell Lung Cancers)
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Review

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26 pages, 2013 KiB  
Review
Tumor Heterogeneity and the Immune Response in Non-Small Cell Lung Cancer: Emerging Insights and Implications for Immunotherapy
by Michael S. Oh, Jensen Abascal, Austin K. Rennels, Ramin Salehi-Rad, Steven M. Dubinett and Bin Liu
Cancers 2025, 17(6), 1027; https://doi.org/10.3390/cancers17061027 - 19 Mar 2025
Viewed by 627
Abstract
Resistance to immune checkpoint inhibitors (ICIs) represents a major challenge for the effective treatment of non-small cell lung cancer (NSCLC). Tumor heterogeneity has been identified as an important mechanism of treatment resistance in cancer and has been increasingly implicated in ICI resistance. The [...] Read more.
Resistance to immune checkpoint inhibitors (ICIs) represents a major challenge for the effective treatment of non-small cell lung cancer (NSCLC). Tumor heterogeneity has been identified as an important mechanism of treatment resistance in cancer and has been increasingly implicated in ICI resistance. The diversity and clonality of tumor neoantigens, which represent the target epitopes for tumor-specific immune cells, have been shown to impact the efficacy of immunotherapy. Advances in genomic techniques have further enhanced our understanding of clonal landscapes within NSCLC and their evolution in response to therapy. In this review, we examine the role of tumor heterogeneity during immune surveillance in NSCLC and highlight its spatial and temporal evolution as revealed by modern technologies. We explore additional sources of heterogeneity, including epigenetic and metabolic factors, that have come under greater scrutiny as potential mediators of the immune response. We finally discuss the implications of tumor heterogeneity on the efficacy of ICIs and highlight potential strategies for overcoming therapeutic resistance. Full article
(This article belongs to the Special Issue Immunotherapy in Non-Small Cell Lung Cancers)
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