Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients—Mechanism of Action and Future Concepts

SIMPLE SUMMARY: Here, we focused on the most important mechanisms of action of combined immunotherapy with modern anticancer approaches in patients with non-small-cell lung cancer. This knowledge is extremely important for lung cancer clinicians. First, it facilitates proper involvement of the patient in the treatment and monitoring its effectiveness. More importantly, the knowledge of the immunotherapy mechanisms will certainly allow quick recognition of the side effects of such a therapy, which are totally different of those observed after chemotherapy. Side effects of combination therapies can occur at any stage of treatment, and even after completion thereof. This review article could particularly explain the mechanism of action of combined immunotherapy, which have different targets in patients. ABSTRACT: Due to the limited effectiveness of immunotherapy used as first-line monotherapy in patients with non-small-cell lung cancer (NSCLC), the concepts of combining classical immunotherapy based on immune checkpoint antibodies with other treatment methods have been developed. Pembrolizumab and atezolizumab were registered in combination with chemotherapy for the treatment of metastatic NSCLC, while durvalumab found its application in consolidation therapy after successful chemoradiotherapy in patients with locally advanced NSCLC. Exceptionally attractive, due to their relatively low toxicity and high effectiveness, are treatment approaches in which a combination of two different immunotherapy methods is applied. This method is based on observations from clinical trials in which nivolumab and ipilimumab were used as first-line therapy for advanced NSCLC. It turned out that the dual blockade of immune checkpoints activated T lymphocytes in different compartments of the immune response, at the same time affecting the downregulation of immune suppressor cells (regulatory T cells). These experiments not only resulted in the registration of combination therapy with nivolumab and ipilimumab, but also initiated other clinical trials using immune checkpoint inhibitors (ICIs) in combination with other ICIs or activators of costimulatory molecules found on immune cells. There are also studies in which ICIs are associated with molecules that modify the tumour environment. This paper describes the mechanism of the synergistic effect of a combination of different immunotherapy methods in NSCLC patients.