ArticleThe Journal of clinical investigation2021
CHI3L1 regulates PD-L1 and anti-CHI3L1-PD-1 antibody elicits synergistic antitumor responses.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 105 citations in OpenAlex.
- Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy.Frontiers in immunology · 2023Trial
- Redefining CHI3L1: Therapeutic Opportunities at the Crossroads of Immune Suppression and Disease Progression.Medicinal research reviews · 2026Review
- EGFR inhibition promotes functional engraftment and graft survival via donor-derived CHI3L1 in fetal RPE suspension transplantation.Cell reports. Medicine · 2026Article
- Bispecific targeting of CHI3L1 and PD-1 as a therapeutic strategy for pulmonary fibrosis.JCI insight · 2026Article
- SYT8 as a potential prognostic biomarker and therapeutic predictor in colorectal cancer: insights from multi-cohort transcriptomic analyses.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Distinct immune landscapes characterize highly versus minimally invasive brain metastases.JCI insight · 2026Article
- Targeting chitinase-3-like protein 2 (CHI3L2) suppresses cell proliferation and migration in glioblastoma.Translational cancer research · 2026Article
- The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination.JCI insight · 2026Article
- Article
- Chitinase-3-like protein 1 depletion in glioma cells alters tumor microenvironment and normalizes neovasculature in human glioma xenografts.Cell communication and signaling : CCS · 2026Article
- Targeting T cell exhaustion in colorectal cancer: emerging roles of LAG-3, TIM-3, and TIGIT signaling in overcoming immunotherapy resistance.Cell communication and signaling : CCS · 2026Review
- Kasugamycin Inhibits Melanoma Lung Metastasis and CHI3L1-Driven M2-Like Tumor-Associated Macrophage Differentiation.ImmunoTargets and therapy · 2026Article
- Lactylated chitinase-3-like protein 1 promotes the development of sepsis.Central-European journal of immunology · 2026Article
- Role of chitinase-3-like protein 1 in liver diseases: A comprehensive review.Genes & diseases · 2025Review
- Up-regulated chitinase-like protein-1 promotes tumour growth while physiological levels are protective.Life science alliance · 2025Article
- Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles.Molecular oncology · 2025Article
- Combination of low-intensity pulsed ultrasound irradiating immune organs with immune checkpoint blockade augments systemic anti-tumor immunity on low tumor burden 4T-1 breast cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Pigmented skin lesions with atypical histopathology indicating a diagnosis of multiple metastases of melanoma: A case report.Oncology letters · 2025Article
- Future Perspectives and Conclusions from Animal Models of CHI3L1-Related Inflammation-Associated Cancer.Cells · 2025Review
- Human chitinases and chitinase-like proteins as emerging drug targets - a medicinal chemistry perspective.RSC medicinal chemistry · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Evasion of the immune response is a hallmark of cancer, and programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) are major mediators of this immunosuppression. Chitinase 3-like 1 (CHI3L1) is induced in many cancers, where it portends a poor prognosis and contributes to tumor metastasis and spread. However, the mechanism(s) that CHI3L1 uses in metastasis have not been defined. Here we demonstrate that CHI3L1 regulates the expression of PD-L1, PD-L2, PD-1, LAG3, and TIM3 and plays a critical role in melanoma progression and lymphatic spread. CHI3L1 also contributed to IFN-γ-stimulated macrophage PD-L1 expression, and RIG-like helicase innate immunity suppressed CHI3L1, PD-L1, and melanoma progression. Individual antibodies against CHI3L1 or PD-1 had discrete antitumor effects and additive antitumor responses in metastasis models and T cell-tumor cell cocultures when administered simultaneously. Synergistic cytotoxic tumor cell death was seen in T cell-tumor cell cocultures, and significantly enhanced antitumor responses were seen in in vivo tumor models treated with bispecific antibodies that simultaneously target CHI3L1 and PD-1. CHI3L1 contributes to tumor progression by stimulating the PD-1/PD-L1 axis and other checkpoint molecules. The simultaneous targeting of CHI3L1 and the PD-1/PD-L1 axis with individual and, more powerfully, with bispecific antibodies represents a promising therapy for pulmonary metastasis and progression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.