Title:Immunotherapy in Non-Small Cell Lung Cancer: Biological Principles and Future Opportunities
Volume: 17
Issue: 8
Author(s): M. Ilie, J. Benzaquen, V. Hofman, S. Lassalle, N. Yazbeck, S. Leroy, S. Heeke, C. Bence, B. Mograbi, N. Glaichenhaus, C.-H. Marquette and P. Hofman*
Affiliation:
- University Cote d'Azur, Inserm U1081/CNRS UMR 7284, Institute for Research on Cancer and Aging, Comprehensive Cancer Center Antoine Lacassagne, Nice,France
Keywords:
NSCLC, immunotherapy, immunosurveillance, immune escape, PD-1, PD-L1.
Abstract: Immunotherapy aims to amplify the anticancer immune response through
reactivation of the lymphocytic response raised against several tumor neo-antigens. To
obtain an effective immune response, this therapeutic approach requires that a number
of immunological checkpoints be passed, such as the activation of excitatory
costimulatory signals or the avoidance of coinhibitory molecules. Among the immune
checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1
has received much attention because of remarkable efficacy in numerous clinical trials
for various cancer types, including non-small cell lung cancer (NSCLC). However,
several limitations exist with these therapeutic agents when used as monotherapy, with
objective responses observed in only 30–40% of patients, with the majority of patients
demonstrating innate resistance, and approximately 25% of responders later
demonstrating disease progression. Recent developments in the understanding of
cancer immunology have the potential to identify mechanisms of innate and acquired
resistance to immune checkpoint inhibitors through translational research in human
samples. This review focuses on the biological basic principles for immunological
checkpoint blockade, and highlights the current status and the perspectives of this
therapeutic approach in NSCLC patients.
