ArticleJournal for immunotherapy of cancer2024
Targeting tumor-associated macrophage-derived CD74 improves efficacy of neoadjuvant chemotherapy in combination with PD-1 blockade for cervical cancer.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Article
- Single-cell and spatial multi-omics reveal mechanistic insights of FOLH1+ endothelial cells in clear cell renal cell carcinoma.Journal of translational medicine · 2026Article
- Heterogeneity of macrophages in PD-1/PD-L1 inhibitor therapy: a single-cell perspective.Cellular & molecular biology letters · 2026Review
- Radiotherapy synergizes with CD24 blockade to initiate macrophage-driven systemic antitumor immunity in non-small cell lung cancer.Experimental hematology & oncology · 2026Article
- Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma.Journal for immunotherapy of cancer · 2026Article
- MIF-CD74 signaling drives immune modulation in medulloblastoma.Neuro-oncology · 2026Article
- scHG: A supercell framework with high-order graph learning enables scalable multi-omics analysis.PLoS computational biology · 2026Article
- TAMs in the Gynecological Tumor Microenvironment: Insights from Cross-Cancer Studies for Immunotherapy.Cancers · 2026Review
- Targeted intestinal barrier repairActa pharmaceutica Sinica. B · 2026Article
- Article
- Molecular Determinants of Macrophage Polarization in Glioblastoma and Implications for Tumor Progression.Cells · 2026Article
- Lactate-induced metabolic reprogramming of TAMs impairs antigen presentation capacity via C/EBPα-CD74 axis in oral squamous cell carcinoma.Clinical and translational medicine · 2026Article
- TiRank prioritizes phenotypic niches in tumor microenvironment for clinical biomarker discovery.Genome medicine · 2026Article
- Advancements in single-cell sequencing for cervical cancer research.Molecular and cellular biochemistry · 2026Review
- Review
- Mitochondrial reprogramming in cervical cancer: crosstalk with tumor immunity, HPV oncogenic signaling, and therapeutic resistance.Frontiers in immunology · 2026Review
- Macrophage polarization in gynecologic malignancies: key signaling pathways and clinical perspectives.Frontiers in immunology · 2026Review
- Cross-scale modeling reveals a TFRC-driven immunosuppressive macrophage niche in cervical cancer.Frontiers in immunology · 2026Article
- Epithelial Cell-Specific Prognostic Signature (FTH1, RIT1, WASL, NDRG2, KIFC3) Stratifies Cervical Cancer Patients and Correlates With Immune Infiltration.Human mutation · 2026Article
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12 authors.
Funding
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Abstract
backgroundCervical cancer has the second-highest mortality rate among malignant tumors of the female reproductive system. Immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) blockade are promising therapeutic agents, but their efficacy when combined with neoadjuvant chemotherapy (NACT) has not been fully tested, and how they alter the tumor microenvironment has not been comprehensively elucidated.
methodsIn this study, we conducted single-cell RNA sequencing using 46,950 cells from nine human cervical cancer tissues representing sequential different stages of NACT and PD-1 blockade combination therapy. We delineated the trajectory of cervical epithelial cells and identified the crucial factors involved in combination therapy. Cell-cell communication analysis was performed between tumor and immune cells. In addition, THP-1-derived and primary monocyte-derived macrophages were cocultured with cervical cancer cells and phagocytosis was detected by flow cytometry. The antitumor activity of blocking CD74 was validated in vivo using a CD74 humanized subcutaneous tumor model.
resultsPathway enrichment analysis indicated that NACT activated cytokine and complement-related immune responses. Cell-cell communication analysis revealed that after NACT therapy, interaction strength between T cells and cancer cells decreased, but intensified between macrophages and cancer cells. We verified that macrophages were necessary for the PD-1 blockade to exert antitumor effects in vitro. Additionally, CD74-positive macrophages frequently interacted with the most immunoreactive epithelial subgroup 3 (Epi3) cancer subgroup during combination NACT. We found that CD74 upregulation limited phagocytosis and stimulated M2 polarization, whereas CD74 blockade enhanced macrophage phagocytosis, decreasing cervical cancer cell viability in vitro and in vivo.
conclusionsOur study reveals the dynamic cell-cell interaction network in the cervical cancer microenvironment influenced by combining NACT and PD-1 blockade. Furthermore, blocking tumor-associated macrophage-derived CD74 could augment neoadjuvant therapeutic efficacy.
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