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Recent Advances of Immunotherapy in Lung Cancer
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Recent Advances of Immunotherapy in Lung Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 12301

Special Issue Editor

Prof. Dr. Federico Cappuzzo

E-Mail Website
Guest Editor
Department of Oncology-Hematology, AUSL della Romagna, Ravenna, Italy
Interests: lung cancer; molecular oncology; targeted therapy; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Lung cancer is still considered the big killer among solid neoplasms, due to the low survival rates after a lung cancer diagnosis. However, in the last decade, the trend of this phenomenon has been reversed thanks also to the advent of immunotherapy. After the brilliant results described in pivotal trials in the metastatic setting, immunotherapy has now emerged as the treatment of choice in most thoracic histologies, even in combination with chemotherapy. Successes in the metastatic setting are also being translated into the curative one, as reported by recent studies in the neo/adjuvant phase or the locally advanced stage. Nonetheless, immunotherapy has a better toxicity profile than chemotherapy or other treatments and this has helped to increase patient quality of life. In this context, there has been significant development in the search for biomarkers that can predict the response to immunotherapy. However, to date, the only factor universally used in clinical practice remains the immunohistochemical expression of programmed death-ligand 1 (PD-L1). This Special Issue is collecting innovative research experiences and new perspectives in the field of immunotherapy in lung cancer.

Prof. Dr. Federico Cappuzzo
Guest Editor

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Keywords

  • NSCLC
  • SCLC
  • Thoracic neoplasms
  • Immunotherapy
  • Checkpoint inhibitors

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Published Papers (3 papers)

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Research

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13 pages, 3782 KiB  
Article
Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer
by Yi-Chun Chao, Kang-Yun Lee, Sheng-Ming Wu, Deng-Yu Kuo, Pei-Wei Shueng and Cheng-Wei Lin
Int. J. Mol. Sci. 2021, 22(11), 5649; https://doi.org/10.3390/ijms22115649 - 26 May 2021
Cited by 23 | Viewed by 5626
Abstract
Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role [...] Read more.
Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC. Full article
(This article belongs to the Special Issue Recent Advances of Immunotherapy in Lung Cancer)
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Review

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23 pages, 802 KiB  
Review
Dissecting Immunotherapy Strategies for Small Cell Lung Cancer: Antibodies, Ionizing Radiation and CAR-T
by Giorgia Guaitoli, Giovanni Neri, Eleonora Cabitza, Salvatore Natalizio, Luciana Mastrodomenico, Sabrina Talerico, Lucia Trudu, Chiara Lauro, Chiara Chiavelli, Maria Cristina Baschieri, Alessio Bruni, Massimo Dominici and Federica Bertolini
Int. J. Mol. Sci. 2022, 23(21), 12728; https://doi.org/10.3390/ijms232112728 - 22 Oct 2022
Cited by 3 | Viewed by 3111
Abstract
Small cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for about 14% of all lung cancers. Platinum-based chemotherapy has been the only available treatment for a long time, until the introduction of immune checkpoint inhibitors (ICIs) recently changed first-line standard [...] Read more.
Small cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for about 14% of all lung cancers. Platinum-based chemotherapy has been the only available treatment for a long time, until the introduction of immune checkpoint inhibitors (ICIs) recently changed first-line standard of care and shed light on the pivotal role of the immune system. Despite improved survival in a subset of patients, a lot of them still do not benefit from first-line chemo-immunotherapy, and several studies are investigating whether different combination strategies (with both systemic and local treatments, such as radiotherapy) may improve patient outcomes. Moreover, research of biomarkers that may be used to predict patients’ outcomes is ongoing. In addition to ICIs, immunotherapy offers other different strategies, including naked monoclonal antibodies targeting tumor associated antigens, conjugated antibody, bispecific antibodies and cellular therapies. In this review, we summarize the main evidence available about the use of immunotherapy in SCLC, the rationale behind combination strategies and the studies that are currently ongoing in this setting, in order to give the reader a clear and complete view of this rapidly expanding topic. Full article
(This article belongs to the Special Issue Recent Advances of Immunotherapy in Lung Cancer)
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13 pages, 3583 KiB  
Review
Immunoprofiling: An Encouraging Method for Predictive Factors Examination in Lung Cancer Patients Treated with Immunotherapy
by Kamila Wojas-Krawczyk, Iwona Paśnik, Tomasz Kucharczyk, Irena Wieleba, Natalia Krzyżanowska, Michał Gil, Paweł Krawczyk and Janusz Milanowski
Int. J. Mol. Sci. 2021, 22(17), 9133; https://doi.org/10.3390/ijms22179133 - 24 Aug 2021
Cited by 6 | Viewed by 2731
Abstract
The efficiency of immunotherapy using monoclonal antibodies that inhibit immune checkpoints has been proven in many clinical studies and well documented by numerous registration approaches. To date, PD-L1 expression on tumor and immune cells, tumor mutation burden (TMB), and microsatellite instability (MSI) are [...] Read more.
The efficiency of immunotherapy using monoclonal antibodies that inhibit immune checkpoints has been proven in many clinical studies and well documented by numerous registration approaches. To date, PD-L1 expression on tumor and immune cells, tumor mutation burden (TMB), and microsatellite instability (MSI) are the only validated predictive factors used for the qualification of cancer patients for immunotherapy. However, they are not the ideal predictive factors. No response to immunotherapy could be observed in patients with high PD-L1 expression, TMB, or MSI. On the other hand, the effectiveness of this treatment method also may occur in patients without PD-L1 expression or with low TMB and with microsatellite stability. When considering the best predictive factor, we should remember that the effectiveness of immunotherapy relies on an overly complex process depending on many factors. To specifically stimulate lymphocytes, not only should their activity in the tumor microenvironment be unlocked, but above all, they should recognize tumor antigens. The proper functioning of the anticancer immune system requires the proper interaction of many elements of the specific and non-specific responses. For these reasons, a multi-parameter analysis of the immune system at its different activity levels is considered a very future-oriented predictive marker. Such complex immunological analysis is performed using modern molecular biology techniques. Based on the gene expression studies, we can determine the content of individual immune cells within the tumor, its stroma, and beyond. This includes all cell types from active memory cytotoxic T cells, M1 macrophages, to exhausted T cells, regulatory T cells, and M2 macrophages. In this article, we summarize the possibilities of using an immune system analysis to predict immunotherapy efficacy in cancer patients. Moreover, we present the advantages and disadvantages of immunoprofiling as well as a proposed future direction for this new method of immune system analysis in cancer patients who receive immunotherapy. Full article
(This article belongs to the Special Issue Recent Advances of Immunotherapy in Lung Cancer)
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