Lung Cancer Therapy: Synergistic Potential of PD-1/PD-L1 and CTLA-4 Inhibitors

Lung cancer is a big challenge for current research because it increases in numbers, day by day with advancement (MDR type of cancer) due to the increase in environmental pollutants and daily life habitual practices of the people like smoking. Lung cancer classifies into non-small-cell lung cancer and small cell lung cancer. It is further subclassified into squamous-cell-carcinoma, large-cell-carcinoma, and lung adenocarcinoma. Day-by-day researchers try to develop new treatment strategy to manage the drug resistance, intracellular accumulation, metastasis, invasion, side effects, and toxicity and develop a more effective personalized novel treatment for the treatment of lung cancer. The current treatment regime depends upon the stage of progression of cancer, the health of the patients, and the affordability during the time of diagnosis. Different pathways can be utilized to treat the lung cancer. T-Cell activation is one of the pathways which can retard the growth of the cancer cells. PD-1 and CTLA-4 inhibitors can modify the signaling pathway and growth of the cancer cell by T-cell activation. PD-1 inhibitors can inhibit immune response and promote self-tolerance by-T-cell activation, antigen-specific T-cell-apoptosis, and regulatory T-cell-apoptosis-inhibition. Similarly, CTLA-4 inhibitors can also function as inhibitory signals by inducing the production of IL-2 and progression of the-cell cycle. CTLA-4 inhibitors stimulate the proliferation of T-cells, mainly in lymph nodes, whereas PD-1 inhibits the-proliferation-of T-cell afterward, primarily in peripheral tissues. The role and application of PD-1 and CTLA-4 inhibitors are explored in this chapter to inhibit the PD-1 and CTLA-4 signaling pathway to manage and treat the lung cancer.