Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

Abstract

Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.

Keywords: cancer vaccination; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); early stage; immune checkpoint inhibitor; immunotherapy; non-small cell lung cancer (NSCLC); programmed death-ligand 1 (PD-L1); surgery.

Figure 1

Mechanism of anti-PD-1/PD-L1 and anti-CTLA-4 ICIs in anti-cancer therapy for NSCLC. Abbreviations: APC, antigen-presenting cell; TCR, T-cell receptor; MHC, major histocompatibility complex; PD-L1, programmed Death-Ligand 1; PD-1, programmed Cell Death Protein-1 (PD-1); CTLA-4, cytotoxic T-lymphocyte-associated protein 4.

Figure 2

To optimize the strategy of pretreatment evaluation, neoadjuvant therapy, surgery, and adjuvant therapy are for early-stage NSCLC. Abbreviations: CT, Computed Tomography; MRI, Magnetic Resonance Imaging; FDG-PET, fluorodeoxyglucose-positron emission tomography; PD-L1, programmed Death-Ligand 1; TMB, tumor mutation burden; HPD, hyperprogressive disease; LDH, lactate dehydrogenase; NLR, neutrophil-to-lymphocyte ratio; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; NSCLC, non-small cell lung cancer; ICIs, immune checkpoint inhibitors.