Cancer Immunotherapy: A Future Paradigm Shift in the Treatment of Non–Small Cell Lung Cancer

Abstract

Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancerinduced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited. Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. The activity of immune checkpoint inhibitors is currently been assessed in treatment-na€ ve patients with PD-L1-positive advanced NSCLC. Combinatorial approaches with other immune checkpoint inhibitors, chemotherapy, or targeted agents are being explored in ongoing clinical trials, and may improve outcome in NSCLC.

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer

“…On the first side, tumour immune microenvironment (TIM) has proved to play a prognostic role in several solid tumours, including LC [5]. This is particularly true for new targeted therapies that modulate tumour-microenvironment cells, expressing programmed cell death protein 1 (PD-1) and its ligand (PD-L1), thereby achieving a substantial tumour regression and prolonged disease stabilisation also in LC patients [6,7].…”

Effect of Cisplatin on the Frequency and Immuno-inhibitory Function of Myeloid-derived Suppressor Cells in A375 Melanoma Model

“…In recent years, immunotherapy has displayed a great promise in the treatment of various tumors (Su et al, 2013;Zhang et al, 2014a;Wang et al, 2014b;Anagnostou et al, 2015;Curti et al, 2015;Swaika et al, 2015). However, the therapeutic activity of immunotherapy is limited by the immunosuppressive factors active in the tumor hosts.…”

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

“…PD-L1 is the best characterized of the two known PD1 ligands and can be expressed by tumor cells as well as by T-and B-cells, macrophages, and dendritic cells [33,34]. Food and Drug Administration (FDA) has approved the use of anti-PD1 mAbs nivolumab and pembrolizumab in metastatic melanoma (in 2014) and non-small cell lung cancer (in 2015), while anti-PD-L1 has demonstrated similar antitumor activities and is currently in a glowing stage of development [35,36].…”