ArticleOncoimmunology
Crk adaptor protein promotes PD-L1 expression, EMT and immune evasion in a murine model of triple-negative breast cancer.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- Multiomic analysis of CCNE1 amplification associated molecular and immune features in gynecological cancers.Discover oncology · 2025Article
- The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL.International journal of molecular sciences · 2025Review
- Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial-Mesenchymal Transition.Cancers · 2025Review
- Immune evasion and resistance in breast cancer.American journal of cancer research · 2025Review
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance.Cancer metastasis reviews · 2024Review
- M1 macrophages induce PD-L1Journal for immunotherapy of cancer · 2023Article
- Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.Genes & diseases · 2023Review
- Heterogeneity and plasticity of epithelial-mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms.Cell proliferation · 2023Review
- Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment.International journal of oncology · 2023Article
- Modulating the tumor microenvironment improves antitumor effect of anti-PD-L1 mAb in breast cancer.BioImpacts : BI · 2023Article
- PD-1/PD-L1 axis in organ fibrosis.Frontiers in immunology · 2023Review
- Camptothesome Potentiates PD-L1 Immune Checkpoint Blockade for Improved Metastatic Triple-Negative Breast Cancer Immunochemotherapy.Molecular pharmaceutics · 2022Article
- Bidirectional crosstalk between epithelial-mesenchymal plasticity and IFNRoyal Society open science · 2022Article
- CD155/SRC complex promotes hepatocellular carcinoma progression via inhibiting the p38 MAPK signalling pathway and correlates with poor prognosis.Clinical and translational medicine · 2022Article
- Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity.Cancers · 2022Review
- Effect of CRISPR/Cas9-Edited PD-1/PD-L1 on Tumor Immunity and Immunotherapy.Frontiers in immunology · 2022Review
- Role of Calcium Homeostasis in Modulating EMT in Cancer.Biomedicines · 2021Review
- Polyphenols Modulating Effects of PD-L1/PD-1 Checkpoint and EMT-Mediated PD-L1 Overexpression in Breast Cancer.Nutrients · 2021Review
- Review
Corrections and comments
- Erratum issuedCorrigendum.2018
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The tumor infiltration of immune cells in solid cancers can profoundly influence host antitumor responses. In recent years, immunotherapeutic regimens, that target immune checkpoints, demonstrated significant antitumor response by increasing intra-tumoral immune cell populations, including CD8+ effector T cells. However, administration of such immune checkpoint inhibitors is largely inefficacious in inducing immunogenicity and treating breast cancer. Currently, there is a great need to better understand cell autonomous mechanisms of immune evasion in breast cancer to identify upstream therapeutic targets that increase the efficacy of immunotherapy. Here we show that Crk, an SH2 and SH3 domain-containing adaptor protein implicated in focal adhesion signaling, cell migration, and invasion, and frequently up-regulated in human cancers, has an important role in regulating the tumor immune microenvironment. Using a murine 4T1 breast adenocarcinoma model of spontaneous metastasis in immune-competent BALB/C mice, we show that genetic ablation of Crk by CRISPR-Cas9 leads to enhanced anti-tumor immune cell populations, cytotoxic effector and immune surveillance cytokines in primary tumor. Pathologically, this leads to a significant reduction in tumor growth and lung metastasis. Mechanistically, Crk KO suppresses EMT and PD-L1 expression on tumor cells and acts additively with anti-PD1 therapy to suppress tumor growth and metastasis outcomes. Taken together, these data reveal a previously un-described function of Crk adaptor protein expression in tumor cells for cell autonomous regulation of tumor immune microenvironment.
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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.