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Review
. 2023 May 30;15(11):2996.
doi: 10.3390/cancers15112996.

Immunotherapy through the Lens of Non-Small Cell Lung Cancer

Robyn Stanley  1 , Saoirse Flanagan  1 , David O' Reilly  2 , Ella Kearney  1 , Jarushka Naidoo  2   3   4 , Catríona M Dowling  1   3
Affiliations
Review

Immunotherapy through the Lens of Non-Small Cell Lung Cancer

Robyn Stanley et al. Cancers (Basel). .

Abstract

Immunotherapy has revolutionised anti-cancer treatment in solid organ malignancies. Specifically, the discovery of CTLA-4 followed by PD-1 in the early 2000s led to the practice-changing clinical development of immune checkpoint inhibitors (ICI). Patients with lung cancer, including both small cell (SCLC) and non-small cell lung cancer (NSCLC), benefit from the most commonly used form of immunotherapy in immune checkpoint inhibitors (ICI), resulting in increased survival and quality of life. In NSCLC, the benefit of ICIs has now extended from advanced NSCLC to earlier stages of disease, resulting in durable benefits and the even the emergence of the word 'cure' in long term responders. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Patients may also develop immune-related toxicity, a small percentage of which is associated with significant mortality and morbidity. This review article highlights the various types of immunotherapeutic strategies, their modes of action, and the practice-changing clinical trials that have led to the widespread use of immunotherapy, with a focus on ICIs in NSCLC and the current challenges associated with advancing the field of immunotherapy.

Keywords: biomarkers; clinical trials; immune checkpoint inhibitors; immune-related adverse events; non-small cell lung cancer.

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Conflict of interest statement

C.M.D. has no reported conflict of interest. J.N. reports the following conflicts of interest: AstraZenca (Research funding, Consulting/Advisory Board, Data Safety Monitoring Board, Honoraria), Bristol Myers Squibb Research funding, Consulting/Advisory Board, Data Safety Monitoring Board, Honoraria), Roche/Genentech (Research funding, Consulting/Advisory Board, Honoraria), Amgen (Research funding, Consulting/Advisory Board), Arcus Biosciences (Research funding, Consulting/Advisory Board/Steering Committee), NGM Pharmaceuticals (Consulting/Advisory Board), Bayer (Consulting/Advisory Board), Regeneron (Consulting/Advisory Board), Takeda (Consulting/Advisory Board), Pfizer (Consulting/Advisory Board), Elevation Oncology (Consulting/Advisory Board), Abbvie (Consulting/Advisory Board), Kaleido Biosciences (Consulting/Advisory Board), Mirati (Research funding), Daiichi Sankyo (Consulting/Advisory Board Data Safety Monitoring Board, Honoraria).

Figures

Figure 1
Figure 1
Mechanisms of action of immune checkpoint inhibitors. T cells recognize tumour antigens at the MHC on antigen presenting cells (APC) by T cell receptors (TCR) displayed on T cells. The interaction between CD80/CD86 (also known as B7-1 or B7-2) on APC and CD28 mediates a T cell co-stimulation in conjugation with TCR signals emitted by the T cell. CTLA-4 on activated T cells interacts with either CD80 or CD86 ligands (with a higher affinity for CD28), thus stopping the T cell from sending inhibitory signal to a T cells. Monoclonal antibodies, anti-CTLA-4 (e.g., ipilimumab) block this inhibitory pathway, thereby restoring T cell activity and amplifying an immune response. Cytotoxic CD8+ specific T cells recognise tumour antigens at the MHC of the APC using TCR. PD-1 is expressed on activated T cells, and the binding of PD-L1 on APC to PD-1 results in an adaptive expression. The interaction between PD-1 and PD-L1 negatively regulates the anti-tumour T cell response and causes immunosuppression. Anti-PD-1 (e.g., pembrolizumab) and anti-PD-L1 mAbs (e.g., atezoliumab) block this inhibitory pathway, thereby restoring T cell activity and relieving the immunosuppression.
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References

    1. Cascone T., Fradette J., Pradhan M., Gibbons D.L. Tumor Immunology and Immunotherapy of Non-Small-Cell Lung Cancer. Cold Spring Harb. Perspect. Med. 2022;12:a037895. doi: 10.1101/cshperspect.a037895. - DOI - PMC - PubMed
    1. Buchbinder E.I., Desai A. CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition. Am. J. Clin. Oncol. 2016;39:98. doi: 10.1097/COC.0000000000000239. - DOI - PMC - PubMed
    1. Berghmans T., Durieux V., Hendriks L.E., Dingemans A.-M. Immunotherapy: From advanced NSCLC to early stages, an evolving concept. Front. Med. 2020;7:90. doi: 10.3389/fmed.2020.00090. - DOI - PMC - PubMed
    1. Tang S., Qin C., Hu H., Liu T., He Y., Guo H., Yan H., Zhang J., Tang S., Zhou H. Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Progress, Challenges, and Prospects. Cells. 2022;11:320. doi: 10.3390/cells11030320. - DOI - PMC - PubMed
    1. Antonia S., Goldberg S.B., Balmanoukian A., Chaft J.E., Sanborn R.E., Gupta A., Narwal R., Steele K., Gu Y., Karakunnel J.J., et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: A multicentre, phase 1b study. Lancet Oncol. 2016;17:299–308. doi: 10.1016/S1470-2045(15)00544-6. - DOI - PMC - PubMed

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