Molecular Landscape of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients With Chinese Advanced Non-small Cell Lung Cancer
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. So the objective of this research is to explore the comprehensive immune molecular markers of primary and acquired resistance to immunotherapy in patients with Chinese advanced NSCLC based on the results of whole exome sequencing (WES) and targeted sequencing (TS)
• Be able to provide informed consent, and understand and agree to follow the research requirements;
• Advanced non-small cell lung cancer;
• Patients receiving immune checkpoint inhibitor treatment represented by anti-PD-1/PD-L1 monoclonal antibody;
• The patient must be able to provide fresh tumor tissue before- and after- ICIs (50mg of tumor tissue sample/ 2 needles of 18G thick needle puncture) or tumor tissue archived within one year (FFPE tissue block or about 15 pieces \[10- 15 sheets\] Freshly cut, unstained FFPE slides) and pathology reports (except for advanced non-small cell lung cancer other than neuroendocrine cancer); provide matched 10mL peripheral whole blood samples at the same time;
• ECOG physical fitness status ≤1;
• The patient must have at least one measurable lesion (assessed according to RECIST v1.1);
• Life expectancy ≥ 12 weeks;
• The patient must have adequate organ function, and must be reached absolute neutrophil count (ANC) ≥1.5x10\^9/L, platelets ≥100x10\^9/L, hemoglobin ≥90g/L, international normalized ratio (INR) or prothrombin time ≤ 1.5x ULN , activated partial thromboplastin time (aPTT)≤1.5x ULN, serum total bilirubin≤1.5x ULN (Patients with Gilbert syndrome can be enrolled if total bilirubin\<3x ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5x ULN(Patient with liver metastases, this standard is AST and ALT≤5x ULN) within 7 days before treatment;