Immunotherapy for lung cancer

Abstract

Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

The role and therapeutic implications of T cells in cancer of the lung

“…37 These findings led to US Food and Drug Administration (FDA) approval of ipilimumab as a first-line therapy for advanced melanoma in 2011. 5,6,25 Preclinical murine studies have corroborated this, with aPD-1 observed to augment antitumor responses and delay metastasis in models of melanoma, colorectal and pancreatic cancer. 2,5 Recently, a phase-II trial investigating tremelimumab, an IgG2 antibody targeting CTLA-4, in patients with relapsed malignant mesothelioma found no significant improvement to survival compared to placebo.…”

“…5,17 Despite this, research indicates these cells may be functionally tolerant to tumor antigen in lung cancer, characterised by dysregulated cytotoxic function and exhaustion. 5,17 Despite this, research indicates these cells may be functionally tolerant to tumor antigen in lung cancer, characterised by dysregulated cytotoxic function and exhaustion.…”

“…17 More recently, resident memory CD8 T-cell (CD103 + ) frequency in early-stage NSCLC correlated with improved prognosis, putatively due to their greater capacity to produce IFNc than other TIL subsets. 5 Other leucocytes associated with tumorderived immunosuppression Lung tumor cells promote an immunosuppressive TME through production of cytokines, including IL-10, vascular endothelial growth factor and TGFb. 5 Other leucocytes associated with tumorderived immunosuppression Lung tumor cells promote an immunosuppressive TME through production of cytokines, including IL-10, vascular endothelial growth factor and TGFb.…”

“…18,25 Further, others have reported that 20-60% of NSCLC tumors were positive for PD-L1 and PD-L2, with overexpression associated unfavourable patient prognosis. 2,5 CURRENT LUNG TUMOR IMMUNOTHERAPY Given the strong evidence supporting the role of the immune system in the development of lung cancer, much research focus has been on the development of various immunotherapies for the disease, especially therapies that enhance T-cellmediated responses. 2,5 CURRENT LUNG TUMOR IMMUNOTHERAPY Given the strong evidence supporting the role of the immune system in the development of lung cancer, much research focus has been on the development of various immunotherapies for the disease, especially therapies that enhance T-cellmediated responses.…”

“…5 However, recent research has challenged this paradigm, demonstrating the immunogenic nature of lung cancer and highlighting the ability of tumors to suppress the immune response within the tumor microenvironment (TME). 5 However, recent research has challenged this paradigm, demonstrating the immunogenic nature of lung cancer and highlighting the ability of tumors to suppress the immune response within the tumor microenvironment (TME).…”