Immune repertoire sequencing reveals differences in treatment response to camrelizumab plus platinum-based chemotherapy in advanced ESCC

TL;DR

This study shows that combining camrelizumab with chemotherapy is effective for advanced esophageal cancer, and immune sequencing reveals differences in immune responses between responders and non-responders.

Contribution

The study introduces immune repertoire sequencing as a tool to understand treatment response mechanisms in ESCC patients receiving camrelizumab plus chemotherapy.

Findings

Camrelizumab plus chemotherapy achieved a 64.8% objective response rate in advanced ESCC patients.

Immune repertoire sequencing revealed significant differences in TCR and BCR CDR3 sequences between responders and non-responders.

Oligoclonal enrichment and specific V/J gene abundance differences were observed in TCR and BCR between groups.

Abstract

This study evaluated the efficacy and safety of camrelizumab combined with platinum-based chemotherapy (taxanes [T] or fluorouracil agents [F] plus platinum [P] drugs) as the first-line treatment in advanced esophageal squamous cell carcinoma (ESCC), using immune repertoire sequencing (IRS) to explore treatment response mechanism. In this multi-center, prospective cohort study, 88 patients received camrelizumab plus TP or FP, achieving a 1-year progression-free survival of 56.8% and overall survival of 68.2%. The objective response rate (ORR) was 64.8%, with a disease control rate of 91.1%. While most treatment-related adverse events were mild, 12.5% of patients experienced grade ≥3 toxicities. IRS showed significant differences in T-cell receptor (TCR) β-chain and immunoglobulin heavy chain between patients with (ORR group) or without ORR (non-ORR group), particularly in the distribution and expression of some genes. Specifically, we found the significant differences in the amino acid composition of complementarity determining region 3 (CDR3) polypeptide sequences in TCR and B-cell receptor (BCR) between the ORR and non-ORR groups. For TCR, we observed substantial oligoclonal enrichment and differences in the abundance of specific V and J genes. Similarly, for BCR, we detected differences in the clonotype abundance of CDR3 polypeptide segments and identified several differential V genes. Camrelizumab combined with platinum-based chemotherapy is effective and well-tolerated as the first-line treatment for ESCC, and IRS may reveal mechanism influencing treatment response.

Figures