Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients
EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive <i>EGFR</i> mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced <i>EG...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/11/2916 |
| _version_ | 1797460067456385024 |
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| author | Dan Yan |
| author_facet | Dan Yan |
| author_sort | Dan Yan |
| collection | DOAJ |
| description | EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive <i>EGFR</i> mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced <i>EGFR</i>-mutant NSCLCs. Although immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs, ICI therapy exhibits limited activity in most <i>EGFR</i>-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in <i>EGFR</i>-mutant NSCLCs contributes to a non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8<sup>+</sup> T cell infiltration, a high number of regulatory CD4<sup>+</sup> T cells, and an increased number of inactivated infiltrated T cells. Additionally, <i>EGFR</i>-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. Promisingly, a small population of <i>EGFR</i>-mutant NSCLCs still durably respond to ICI therapy. The hope of ICI therapy from pre-clinical studies and clinical trials is reviewed in <i>EGFR</i>-mutant NSCLCs. The challenges of application ICI therapy in <i>EGFR</i>-mutant NSCLCs are also reviewed. |
| first_indexed | 2024-03-09T17:00:51Z |
| format | Article |
| id | doaj.art-b1b9b7beb04549658993597409a54f64 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:00:51Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b1b9b7beb04549658993597409a54f642023-11-24T14:30:42ZengMDPI AGBiomedicines2227-90592023-10-011111291610.3390/biomedicines11112916Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC PatientsDan Yan0Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Atlanta, GA 30322, USAEGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive <i>EGFR</i> mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced <i>EGFR</i>-mutant NSCLCs. Although immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs, ICI therapy exhibits limited activity in most <i>EGFR</i>-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in <i>EGFR</i>-mutant NSCLCs contributes to a non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8<sup>+</sup> T cell infiltration, a high number of regulatory CD4<sup>+</sup> T cells, and an increased number of inactivated infiltrated T cells. Additionally, <i>EGFR</i>-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. Promisingly, a small population of <i>EGFR</i>-mutant NSCLCs still durably respond to ICI therapy. The hope of ICI therapy from pre-clinical studies and clinical trials is reviewed in <i>EGFR</i>-mutant NSCLCs. The challenges of application ICI therapy in <i>EGFR</i>-mutant NSCLCs are also reviewed.https://www.mdpi.com/2227-9059/11/11/2916non-small cell lung cancer<i>EGFR</i> mutationimmunotherapy |
| spellingShingle | Dan Yan Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients Biomedicines non-small cell lung cancer <i>EGFR</i> mutation immunotherapy |
| title | Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients |
| title_full | Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients |
| title_fullStr | Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients |
| title_full_unstemmed | Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients |
| title_short | Hope and Challenges: Immunotherapy in <i>EGFR</i>-Mutant NSCLC Patients |
| title_sort | hope and challenges immunotherapy in i egfr i mutant nsclc patients |
| topic | non-small cell lung cancer <i>EGFR</i> mutation immunotherapy |
| url | https://www.mdpi.com/2227-9059/11/11/2916 |
| work_keys_str_mv | AT danyan hopeandchallengesimmunotherapyiniegfrimutantnsclcpatients |