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Cancers
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Precision Immuno-Oncology in NSCLC
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Precision Immuno-Oncology in NSCLC

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

Deadline for manuscript submissions: closed (8 February 2024) | Viewed by 11655

Special Issue Editor

Dr. Laura Mezquita

E-Mail Website
Guest Editor
1. Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Medical Oncology Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain
2. Department of Medicine, University of Barcelona, 08007 Barcelona, Spain
Interests: non-small cell lung cancer; biomarkers; immune checkpoint inhibitor; lung cancer

Special Issue Information

Dear Colleagues,

NSCLC is a major public health problem, being the first cause of cancer death worldwide. Precision immuno-oncology involves identifying unique biomarkers that can improve the treatment selection of immunotherapy strategies. Through the comprehensive characterization of a patient's immune system (host), tumor profile and the interactions in the tumor microenvironment (TME), researchers and clinicians can develop personalized therapeutic plans. This approach is particularly exciting because it offers the potential for long-term outcomes in patients who may have previously had limited therapeutic options.

Recent advances in genomic, transcriptomic sequencing and other diagnostic technologies, including the immune characterization of circulating and tumor immune markers, have made precision immuno-oncology research possible. Scientists are now able to identify these tumor- and host-related biomarkers in lung cancer cells that provide clinically relevant information for treatment selection. This personalized approach to treatment will revolutionize cancer care and may lead to more effective and less toxic treatments for patients with NSCLC.

Overall, precision immuno-oncology in NSCLC research is an exciting and promising field of study. This Special Issue will delve into the science of immunotherapy and its application in the precision treatment of non-small cell lung cancer to help deepen our understanding of the disease and accelerate the development of new therapies.

Dr. Laura Mezquita
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

  • NSCLC
  • lung cancer
  • immunology
  • biomarkers
  • immunotherapy
  • tumor microenvironment
  • immune cells
  • molecular profiling

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Published Papers (6 papers)

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Research

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16 pages, 2549 KiB  
Article
Longitudinal Study of Advanced Non-Small Cell Lung Cancer with Initial Durable Clinical Benefit to Immunotherapy: Strategies for Anti-PD-1/PD-L1 Continuation beyond Progression
by Ivan Pourmir, Reza Elaidi, Zineb Maaradji, Hortense De Saint Basile, Monivann Ung, Mohammed Ismaili, Laure Fournier, Bastien Rance, Laure Gibault, Rym Ben Dhiab, Benoit Gazeau and Elizabeth Fabre
Cancers 2023, 15(23), 5587; https://doi.org/10.3390/cancers15235587 - 26 Nov 2023
Viewed by 1423
Abstract
Background and aim: A better understanding of resistance to checkpoint inhibitors is essential to define subsequent treatments in advanced non-small cell lung cancer. By characterizing clinical and radiological features of progression after anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1), we aimed to define therapeutic strategies [...] Read more.
Background and aim: A better understanding of resistance to checkpoint inhibitors is essential to define subsequent treatments in advanced non-small cell lung cancer. By characterizing clinical and radiological features of progression after anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1), we aimed to define therapeutic strategies in patients with initial durable clinical benefit. Patients and methods: This monocentric, retrospective study included patients who presented progressive disease (PD) according to RECIST 1.1 criteria after anti-PD-1/PD-L1 monotherapy. Patients were classified into two groups, “primary resistance” and “Progressive Disease (PD) after Durable Clinical Benefit (DCB)”, according to the Society of Immunotherapy of Cancer classification. We compared the post-progression survival (PPS) of both groups and analyzed the patterns of progression. An exploratory analysis was performed using the tumor growth rate (TGR) to assess the global growth kinetics of cancer and the persistent benefit of immunotherapy beyond PD after DCB. Results: A total of 148 patients were included; 105 of them presented “primary resistance” and 43 “PD after DCB”. The median PPS was 5.2 months (95% CI: 2.6–6.5) for primary resistance (p < 0.0001) vs. 21.3 months (95% CI: 18.5–36.3) for “PD after DCB”, and the multivariable hazard ratio was 0.14 (95% CI: 0.07–0.30). The oligoprogression pattern was frequent in the “PD after DCB” group (76.7%) and occurred mostly in pre-existing lesions (72.1%). TGR deceleration suggested a persistent benefit of PD-1/PD-L1 blockade in 44.2% of cases. Conclusions: PD after DCB is an independent factor of longer post-progression survival with specific patterns that prompt to contemplate loco-regional treatments. TGR is a promising tool to assess the residual benefit of immunotherapy and justify the continuation of immunotherapy in addition to radiotherapy or surgery. Full article
(This article belongs to the Special Issue Precision Immuno-Oncology in NSCLC)
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13 pages, 1805 KiB  
Article
Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations
by Soojin Jun, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Juhee Cho and Hyun Ae Jung
Cancers 2023, 15(22), 5450; https://doi.org/10.3390/cancers15225450 - 16 Nov 2023
Cited by 2 | Viewed by 1867
Abstract
Introduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with [...] Read more.
Introduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with diverse AGAs and verify the predictive biomarkers of ICI efficacy. Methods: From January 2018 to July 2022, this study compared the progression-free survival (PFS) of NSCLC patients with different AGAs treated with ICI monotherapy as second- or later-line therapy at Samsung Medical Center. To ascertain the predictors of ICIs efficacy, we adjusted ICIs’ effects on PFS in terms of clinical and molecular biomarkers. Results: EGFR (46.0%) was the most prevalent mutation in 324 patients. In multivariate analysis, PD-L1 positivity (tumor proportion score (TPS) ≥ 1%) (HR = 0.41) and the use of steroids for immune-related adverse events (HR = 0.46) were positive factors for ICI therapy in the AGAs group. Co-existing mutation of STK11 with KRAS mutation (HR = 4.53) and TP53 with MET mutation (HR = 9.78) was negatively associated with survival. Conclusions: The efficacy of ICI treatment varied across AGA subtypes, but patients with KRAS, MET, and BRAF mutations demonstrated relatively long-duration benefits of ICI therapy. PD-L1 was a significant positive predictive biomarker in all AGA groups. Full article
(This article belongs to the Special Issue Precision Immuno-Oncology in NSCLC)
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19 pages, 9227 KiB  
Article
Computed Tomography-Based Quantitative Texture Analysis and Gut Microbial Community Signatures Predict Survival in Non-Small Cell Lung Cancer
by David Dora, Glen J. Weiss, Zsolt Megyesfalvi, Gabriella Gállfy, Edit Dulka, Anna Kerpel-Fronius, Judit Berta, Judit Moldvay, Balazs Dome and Zoltan Lohinai
Cancers 2023, 15(20), 5091; https://doi.org/10.3390/cancers15205091 - 21 Oct 2023
Cited by 1 | Viewed by 2210
Abstract
This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients by analyzing their CT scans (n = 129) and [...] Read more.
This study aims to combine computed tomography (CT)-based texture analysis (QTA) and a microbiome-based biomarker signature to predict the overall survival (OS) of immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients by analyzing their CT scans (n = 129) and fecal microbiome (n = 58). One hundred and five continuous CT parameters were obtained, where principal component analysis (PCA) identified seven major components that explained 80% of the data variation. Shotgun metagenomics (MG) and ITS analysis were performed to reveal the abundance of bacterial and fungal species. The relative abundance of Bacteroides dorei and Parabacteroides distasonis was associated with long OS (>6 mo), whereas the bacteria Clostridium perfringens and Enterococcus faecium and the fungal taxa Cortinarius davemallochii, Helotiales, Chaetosphaeriales, and Tremellomycetes were associated with short OS (≤6 mo). Hymenoscyphus immutabilis and Clavulinopsis fusiformis were more abundant in patients with high (≥50%) PD-L1-expressing tumors, whereas Thelephoraceae and Lachnospiraceae bacterium were enriched in patients with ICI-related toxicities. An artificial intelligence (AI) approach based on extreme gradient boosting evaluated the associations between the outcomes and various clinicopathological parameters. AI identified MG signatures for patients with a favorable ICI response and high PD-L1 expression, with 84% and 79% accuracy, respectively. The combination of QTA parameters and MG had a positive predictive value of 90% for both therapeutic response and OS. According to our hypothesis, the QTA parameters and gut microbiome signatures can predict OS, the response to therapy, the PD-L1 expression, and toxicity in NSCLC patients treated with ICI, and a machine learning approach can combine these variables to create a reliable predictive model, as we suggest in this research. Full article
(This article belongs to the Special Issue Precision Immuno-Oncology in NSCLC)
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Review

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15 pages, 1046 KiB  
Review
Precision Immuno-Oncology in NSCLC through Gender Equity Lenses
by Jennifer Marks, Arthi Sridhar, Angela Ai, Lauren Kiel, Rebekah Kaufman, Oyepeju Abioye, Courtney Mantz and Narjust Florez
Cancers 2024, 16(7), 1413; https://doi.org/10.3390/cancers16071413 - 4 Apr 2024
Cited by 1 | Viewed by 1761
Abstract
Precision immuno-oncology involves the development of personalized cancer treatments that are influenced by the unique nature of an individual’s DNA, immune cells, and their tumor’s molecular characterization. Biological sex influences immunity; females typically mount stronger innate and adaptive immune responses than males. Though [...] Read more.
Precision immuno-oncology involves the development of personalized cancer treatments that are influenced by the unique nature of an individual’s DNA, immune cells, and their tumor’s molecular characterization. Biological sex influences immunity; females typically mount stronger innate and adaptive immune responses than males. Though more research is warranted, we continue to observe an enhanced benefit for females with lung cancer when treated with combination chemoimmunotherapy in contrast to the preferred approach of utilizing immunotherapy alone in men. Despite the observed sex differences in response to treatments, women remain underrepresented in oncology clinical trials, largely as a result of gender-biased misconceptions. Such exclusion has resulted in the development of less efficacious treatment guidelines and clinical recommendations and has created a knowledge gap in regard to immunotherapy-related survivorship issues such as fertility. To develop a more precise approach to care and overcome the exclusion of women from clinical trials, flexible trial schedules, multilingual communication strategies, financial, and transportation assistance for participants should be adopted. The impact of intersectionality and other determinants of health that affect the diagnosis, treatment, and outcomes in women must also be considered in order to develop a comprehensive understanding of the unique impact of immunotherapy in all women with lung cancer. Full article
(This article belongs to the Special Issue Precision Immuno-Oncology in NSCLC)
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22 pages, 719 KiB  
Review
Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer
by Marco Siringo, Javier Baena, Helena Bote de Cabo, Javier Torres-Jiménez, María Zurera, Jon Zugazagoitia and Luis Paz-Ares
Cancers 2023, 15(23), 5505; https://doi.org/10.3390/cancers15235505 - 21 Nov 2023
Cited by 3 | Viewed by 2199
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their long-term benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody–drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-be-published phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives. Full article
(This article belongs to the Special Issue Precision Immuno-Oncology in NSCLC)
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16 pages, 659 KiB  
Review
Advancing Understanding of Non-Small Cell Lung Cancer with Multiplexed Antibody-Based Spatial Imaging Technologies
by Simon Gray and Christian H. Ottensmeier
Cancers 2023, 15(19), 4797; https://doi.org/10.3390/cancers15194797 - 29 Sep 2023
Cited by 2 | Viewed by 1529
Abstract
Non-small cell lung cancer (NSCLC) remains a cause of significant morbidity and mortality, despite significant advances made in its treatment using immune checkpoint inhibitors (ICIs) over the last decade; while a minority experience prolonged responses with ICIs, benefit is limited for most patients. [...] Read more.
Non-small cell lung cancer (NSCLC) remains a cause of significant morbidity and mortality, despite significant advances made in its treatment using immune checkpoint inhibitors (ICIs) over the last decade; while a minority experience prolonged responses with ICIs, benefit is limited for most patients. The development of multiplexed antibody-based (MAB) spatial tissue imaging technologies has revolutionised analysis of the tumour microenvironment (TME), enabling identification of a wide range of cell types and subtypes, and analysis of the spatial relationships and interactions between them. Such study has the potential to translate into a greater understanding of treatment susceptibility and resistance, factors influencing prognosis and recurrence risk, and identification of novel therapeutic approaches and rational treatment combinations to improve patient outcomes in the clinic. Herein we review studies that have leveraged MAB technologies to deliver novel insights into the TME of NSCLC. Full article
(This article belongs to the Special Issue Precision Immuno-Oncology in NSCLC)
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