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

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) b-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 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
mechanisms influencing treatment response.