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

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.

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

“…As one of the cancers with a lower survival rate, lung cancer has been challenged with many different trials with new generations of chemical drugs and promising immunotherapeutic approaches with antibodies to lead to the successful treatment of this tumor [ 60 , 61 ]. Among them, drug intervention is also a hot spot in lung cancer treatment [ 62 ].…”

The Effectiveness of Cancer Immune Checkpoint Inhibitor Retreatment and Rechallenge—A Systematic Review

“…PD-1 and CTLA-4 are receptors located on T cells which may be bound by their upregulated cognate ligands expressed on tumour cell surfaces, thus suppressing the anti-tumoral immune response. ICIs work by the blockage of their interaction that leads to restoration of cytotoxic T lymphocyte function both in the tumour microenvironment (TME) and in peripheral tissue, which contributes to better therapeutic outcomes [ 3 , 4 , 5 ]. Their efficacy was initially observed in numerous clinical trials, outperforming or augmenting previously introduced oncological regimens [ 6 , 7 , 8 , 9 ].…”