Work

Intra-tumoural RAMP1+ B cells promote resistance to neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma

Year: 2024

Type: article

Abstract: Introduction The application of neoadjuvant immunotherapy in oesophageal squamous cell carcinoma (ESCC) reactivates anti-tumour immune responses and prolong postoperative survival. However, due to the heterogeneity of tumour microenvironment, limited patients have achieved pathological regression after treatment. The dual roles of B cells were recently highlighted in ESCC. The study aimed to investigate the role of B cell subclusters and the upstream signalling of B cell differentiation in ESCC resistant to immunotherapy. Methods Single-cell RNA sequencing was employed for ESCC specimens with distinct responses to neoadjuvant immunotherapy to map the landscape of intra-tumoural B cells. Results A novel subset of neuropeptide receptor, receptor activity-modifying protein 1 (RAMP1) positive B cells was revealed to accumulate in ESCC that is resistant to neoadjuvant immunotherapy. Stimulated by nociceptor neurons secreting calcitonin gene-related peptide (CGRP), RAMP1(+) B cells exhibit an immunosuppressive phenotype. The elevated secretion of immune-regulating cytokines by RAMP1(+) B cells blunts the cytotoxicity of Cluster of Differentiation (CD)8(+) T cell and leads to tumour immune evasion. A combination of RAMP1 blocker and anti-Programmed cell death protein (PD)-1 therapies synergistically reinvigorated anti-tumour immunity, reducing tumour progression in vitro. Conclusion The study suggests that RAMP1(+) B cells play a critical role in mediating resistance to neoadjuvant immunotherapy in ESCC. Targeting the CGRP-RAMP axis remodels B cells and enhance the efficacy of current immunotherapies, providing new strategies for overcoming treatment resistance.

Source: Immunotherapy Advances

DOI: 10.1093/immadv/ltaf012

Authors: Hongyu Zhang, Yuchen Zhang, Pingjing Zhou, Yifan Guo, Liqun Jiang, Jie Gu

Institutions: Shanghai Medical College of Fudan University, Fudan University, Zhongshan Hospital, Yangzhou University

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,107