Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance
Despite the relevant antitumor efficacy of immunotherapy in advanced non-small cell lung cancer (NSCLC), the results in patients whose cancer harbors activating epidermal growth factor receptor (EGFR) mutations are disappointing. The biological mechanisms underlying immune escape and both unresponsi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01479/full |
| _version_ | 1829492038143311872 |
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| author | Anna Passarelli Michele Aieta Alessandro Sgambato Cesare Gridelli |
| author_facet | Anna Passarelli Michele Aieta Alessandro Sgambato Cesare Gridelli |
| author_sort | Anna Passarelli |
| collection | DOAJ |
| description | Despite the relevant antitumor efficacy of immunotherapy in advanced non-small cell lung cancer (NSCLC), the results in patients whose cancer harbors activating epidermal growth factor receptor (EGFR) mutations are disappointing. The biological mechanisms underlying immune escape and both unresponsiveness and resistance to immunotherapy in EGFR-mutant NSCLC patients have been partially investigated. To this regard, lung cancer immune escape largely involves high amounts of adenosine within the tumor milieu with broad immunosuppressive effects. Indeed, besides immune checkpoint receptors and their ligands, other mechanisms inducing immunosuppression and including adenosine produced by ecto-nucleotidases CD39 and CD73 contribute to lung tumorigenesis and progression. Here, we review the clinical results of immune checkpoint inhibitors in EGFR-mutant NSCLC, focusing on the dynamic immune composition of EGFR-mutant tumor microenvironment. The adenosine pathway-mediated dysregulation of energy metabolism in tumor microenvironment is suggested as a potential mechanism involved in the immune escape process. Finally, we report the strong rationale for planning strategies of combination therapy with immune checkpoints blockade and adenosine signaling inhibition to overcome immune escape and immunotherapy resistance in EGFR-mutated NSCLC. |
| first_indexed | 2024-12-15T00:48:51Z |
| format | Article |
| id | doaj.art-75bc51ebb5314e41b84cd5bbdbf4f44c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-15T00:48:51Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-75bc51ebb5314e41b84cd5bbdbf4f44c2022-12-21T22:41:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01479560840Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune ResistanceAnna Passarelli0Michele Aieta1Alessandro Sgambato2Cesare Gridelli3Unit of Medical Oncology, Department of Onco-Hematology, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, ItalyUnit of Medical Oncology, Department of Onco-Hematology, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, ItalyLaboratory of Pre-clinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, ItalyDivision of Medical Oncology, “S.G. Moscati” Hospital, Avellino, ItalyDespite the relevant antitumor efficacy of immunotherapy in advanced non-small cell lung cancer (NSCLC), the results in patients whose cancer harbors activating epidermal growth factor receptor (EGFR) mutations are disappointing. The biological mechanisms underlying immune escape and both unresponsiveness and resistance to immunotherapy in EGFR-mutant NSCLC patients have been partially investigated. To this regard, lung cancer immune escape largely involves high amounts of adenosine within the tumor milieu with broad immunosuppressive effects. Indeed, besides immune checkpoint receptors and their ligands, other mechanisms inducing immunosuppression and including adenosine produced by ecto-nucleotidases CD39 and CD73 contribute to lung tumorigenesis and progression. Here, we review the clinical results of immune checkpoint inhibitors in EGFR-mutant NSCLC, focusing on the dynamic immune composition of EGFR-mutant tumor microenvironment. The adenosine pathway-mediated dysregulation of energy metabolism in tumor microenvironment is suggested as a potential mechanism involved in the immune escape process. Finally, we report the strong rationale for planning strategies of combination therapy with immune checkpoints blockade and adenosine signaling inhibition to overcome immune escape and immunotherapy resistance in EGFR-mutated NSCLC.https://www.frontiersin.org/article/10.3389/fimmu.2020.01479/fullnon-small cell lung cancerepidermal growth factor receptorimmune metabolismadenosineCD73immunotherapy |
| spellingShingle | Anna Passarelli Michele Aieta Alessandro Sgambato Cesare Gridelli Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance Frontiers in Immunology non-small cell lung cancer epidermal growth factor receptor immune metabolism adenosine CD73 immunotherapy |
| title | Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance |
| title_full | Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance |
| title_fullStr | Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance |
| title_full_unstemmed | Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance |
| title_short | Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance |
| title_sort | targeting immunometabolism mediated by cd73 pathway in egfr mutated non small cell lung cancer a new hope for overcoming immune resistance |
| topic | non-small cell lung cancer epidermal growth factor receptor immune metabolism adenosine CD73 immunotherapy |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01479/full |
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