ArticleImmunotherapy advances2025
Intra-tumoural RAMP1+ B cells promote resistance to neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma.
Article in Immunotherapy advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Mechanisms of neuropeptide-mediated immune sensing in the modulation of antitumor immunity.Journal for immunotherapy of cancer · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Radiotherapy-Associated Pain in Head and Neck Cancer: From Clinical Burden to Neuroimmune Modulator.Journal of clinical medicine · 2026Review
- Harnessing the duality of regulatory B cells: from identification of characteristic molecules to therapeutic targeting.Immunotherapy advances · 2026Article
- Neuro-immune cross-talk in cancer.Nature reviews. Cancer · 2025Review
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Authors and funding
6 authors.
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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 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.
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