Sugar Chain Markers for Immunotherapy Resistance in Chinese NSCLC Patients

Immunotherapy has improved the prognosis of non-small cell lung cancer (NSCLC) patients, but about 80% of patients do not respond at all, which is called primary resistance. Absence of the PD-L1 expression is regarded as one of primary resistant reasons to immunotherapy, there are some other reasons which have been reported to be related with the primary resistance, including tumor mutation burden (TMB), microsatellite instability (MSI), tumor neoantigen burden (TNB), HLA genotype, loss of heterozygosity (LOH), intra tumoral heterogeneity (ITH), genome wide doubling (WGD), and ploidy. While some patients initially respond to immunotherapy, later relapse and develop disease progression, which is called acquired resistance, like escaping of interferon signaling pathways or mutations in some important genes such as B2M/JAK1/JAK2. Sugar chains, as the third chain of life except nucleic acids and proteins. More than half of the proteins in the human body have sugar chain modifications. During the occurrence, development, and metastasis of malignant tumors such as lung cancer, colorectal cancer, and gastric cancer, protein glycosylation undergoes corresponding changes as the disease progresses. Discovering and elucidating disease-related glycoproteins and their characteristic sugar chains is of great significance for searching for disease-specific biomarkers. So the objective of this research is to explore the comprehensive characteristic sugar chain markers of primary and acquired resistance to immunotherapy in patients with Chinese advanced NSCLC.