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Review
. 2024 Oct 25;16(21):3603.
doi: 10.3390/cancers16213603.

Novel Immunotherapeutics for the Treatment of Non-Small Cell Lung Cancer (NSCLC) Resistant to PD-1/PD-L1 Inhibitors

Jyoti Malhotra  1 , Amy Huang  2 , Arya Amini  3 , Percy Lee  3
Affiliations
Review

Novel Immunotherapeutics for the Treatment of Non-Small Cell Lung Cancer (NSCLC) Resistant to PD-1/PD-L1 Inhibitors

Jyoti Malhotra et al. Cancers (Basel). .

Abstract

Immunotherapy with PD-1/PD-L1 inhibitors is the standard method of care for the treatment of newly diagnosed advanced or metastatic NSCLC, with or without chemotherapy. Many tumors, however, develop resistance to these immunotherapy agents. There is a need to develop more effective therapies for patients with metastatic NSCLC in the second-line setting and beyond. In this review, we present an overview of novel immunotherapies being investigated regarding the treatment of these patients. We summarize completed, as well as ongoing, trials investigating these therapies as monotherapy or in combination with PD-1/PD-L1 inhibitors. These include immune co-stimulatory antibodies, T-cell agonists, oncolytic viruses, vaccines, TIL therapies, and CAR-T therapies.

Keywords: immunotherapy; resistance; trials.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Therapeutic approaches for PD1/PD-L1-resistant NSCLC.
See this image and copyright information in PMC

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References

    1. Kluger H.M., Tawbi H.A., Ascierto M.L., Bowden M., Callahan M.K., Cha E., Chen H.X., Drake C.G., Feltquate D.M., Ferris R.L., et al. Defining tumor resistance to PD-1 pathway blockade: Recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce. J. Immunother. Cancer. 2020;8:e000398. doi: 10.1136/jitc-2019-000398. - DOI - PMC - PubMed
    1. Uryvaev A., Passhak M., Hershkovits D., Sabo E., Bar-Sela G. The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma. Med. Oncol. 2018;35:25. doi: 10.1007/s12032-018-1080-0. - DOI - PubMed
    1. Tumeh P.C., Harview C.L., Yearley J.H., Shintaku I.P., Taylor E.J., Robert L., Chmielowski B., Spasic M., Henry G., Ciobanu V., et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–571. doi: 10.1038/nature13954. - DOI - PMC - PubMed
    1. Snyder A., Makarov V., Merghoub T., Yuan J., Zaretsky J.M., Desrichard A., Walsh L.A., Postow M.A., Wong P., Ho T.S., et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 2014;371:2189–2199. doi: 10.1056/NEJMoa1406498. - DOI - PMC - PubMed
    1. Ayers M., Lunceford J., Nebozhyn M., Murphy E., Loboda A., Kaufman D.R., Albright A., Cheng J.D., Kang S.P., Shankaran V., et al. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Investig. 2017;127:2930–2940. doi: 10.1172/JCI91190. - DOI - PMC - PubMed

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