PD-1+ mast cell enhanced by PD-1 blocking therapy associated with resistance to immunotherapy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36018370", "kind": "science-record", "revision": 3, "content_hash": "sha256:d9a7a0dc3433bab526a51a67104be66b646a5d01825ac13f40625cb2f97c106a", "created_at": "2026-11-01T18:15:10Z", "updated_at": "2026-11-01T21:28:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PD-1+ mast cell enhanced by PD-1 blocking therapy associated with resistance to immunotherapy.", "doi": "10.1007/s00262-022-03282-6", "pmid": "36018370", "authors": ["Jun Li", "Gang Peng", "Kuikui Zhu", "Xiaohua Jie", "Yingzhuo Xu", "Xinrui Rao", "Yunhong Xu", "Yunshang Chen", "Biyuan Xing", "Gang Wu", "Liangliang Shi"], "journal": "Cancer immunology, immunotherapy : CII", "year": 2023, "abstract": "BACKGROUND: Programmed cell death protein 1 (PD-1) antibody has been approved for a variety of tumors, but its effective rate is unsatisfactory. New evidence suggests that mast cells are an important component of the tumor microenvironment and are associated with resistance to immunotherapy, but the underlying mechanism is not clear.\nMETHODS: Bioinformatics analysis of patients with melanoma in TCGA-SKCM and GSE91061 was used to determine the prognostic value of mast cells and their association with anti-PD-1 immunotherapy. HMC-1 cells (mast cell line) and bone marrow-derived mast cells (BMMCs) were used to verify the effect of PD-1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to verify the effect of the PD-1 antibody on mast cells in vivo.\nRESULTS: Bioinformatics analysis showed that mast cells were a poor prognostic factor associated with resistance to anti-PD-1 immunotherapy. PD-1 was expressed on the mast cell membrane. The PD-1 antibody promoted the release of histamine and cytokines from mast cells via the PI3K/AKT pathway and calcium signaling pathway. The activation of mast cells induced by PD-1 antibody could be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of PD-1 antibody and decreased the infiltration of mast cells and the density of microvessels.\nCONCLUSION: PD-1+ mast cell activated by PD-1 antibody plays a negative role in the tumor microenvironment via the enhanced function of releasing histamine and cytokines. Inhibition of mast cell may provide a new solution to solve the low response rate of anti-PD-1 immunotherapy.", "claims": [{"id": "claim-method", "statement": "The CIBERSORT algorithm was used to process the transcriptome data to calculate the abundance of activated mast cell in each tumor sample.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36018370", "locator": "sections[21] \"Activated mast cell is associated with poor prognosis and immunotherapy resistance in melanoma\" paragraph 2", "quote": "The CIBERSORT algorithm was used to process the transcriptome data to calculate the abundance of activated mast cell in each tumor sample."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The transcriptome data and clinical information of 407 patients in TCGA-SKCM were derived from The Cancer Genome Atlas (TCGA, https://www.cancer.gov/tcga).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36018370", "locator": "sections[3] \"Patients\" paragraph 2", "quote": "The transcriptome data and clinical information of 407 patients in TCGA-SKCM were derived from The Cancer Genome Atlas (TCGA, https://www.cancer.gov/tcga)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Mast cell activation is associated with poor prognosis and immunotherapy resistance in melanoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36018370", "locator": "sections[21] \"Activated mast cell is associated with poor prognosis and immunotherapy resistance in melanoma\" paragraph 3", "quote": "Taken together, these findings suggest that mast cell activation is associated with poor prognosis and immunotherapy resistance in melanoma."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Mast cell activation is associated with poor prognosis and immunotherapy resistance in melanoma.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36018370"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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RESULTS: Bioinformatics analysis showed tha", "d be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of P", "1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to veri", "en the diameter of the tumor was 5–9 mm, the mice were randomly divided into four groups. There wer"], "order_basis": "paper_text_order:734", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ican Type Culture Collection (ATCC). The two cell lines were cultured in 1640 complete medium (10% fetal bovine se", "e Collection (ATCC). The two cell lines were cultured in 1640 complete medium (10% fetal bovine serum"], "order_basis": "paper_text_order:2358", "id": "assay:2"}]}