ArticleMolecular cancer2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03502330 (A Phase I/Ib Study of APX005M in Combination With Nivolumab and Cabiralizumab in Patients With Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma Whose Disease Has Progressed on Anti-PD- 1/PD-L1 Therapy), which is not on this map. Cited by 14 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.
A Phase I/Ib Study of APX005M in Combination With Nivolumab and Cabiralizumab in Patients With Advanced Melanoma, Non-small Cell Lung Cancer or Renal Cell Carcinoma Whose Disease Has Progressed on Anti-PD- 1/PD-L1 Therapy
Who cites it
14 citing papers in PubMed, 11 citations in OpenAlex.
- A phase 2 trial of CXCR4 antagonism and PD1 inhibition in metastatic pancreatic adenocarcinoma reveals recruitment of T cells but also immunosuppressive macrophages.Oncoimmunology · 2025Trial
- Development of [111In]In-CHX-A″-DTPA-αCD68 for ImmunoSPECT to Image Murine Macrophages.Molecular pharmaceutics · 2026Article
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- CD40 agonism in renal cell carcinoma enhances immune checkpoint activity through myeloid cells.iScience · 2026Article
- CD40 Agonist Therapy in Melanoma: Translating Preclinical Promise Into Clinical Practice.Pigment cell & melanoma research · 2026Review
- Subtype-Specific Prognosis, Recurrence Patterns, and Molecular Features in 148 Chinese Uterine Sarcomas: A Real-World Study.Cancers · 2026Article
- Harnessing Inflammatory Monocytes to Overcome Resistance to Anti-PD-1 Immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Deciphering immunosuppressive niches by spatial single-cell proteomics: spatial interaction networks and translational opportunities.Frontiers in immunology · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges.Essays in biochemistry · 2025Review
- The mechanism of action and therapeutic potential of tumor-associated macrophages in tumor immune evasion.Frontiers in immunology · 2025Review
- M1 macrophages - unexpected contribution to tumor progression.Frontiers in immunology · 2025Review
- Reprogramming Tumor-Associated Macrophage Using Nanocarriers: New Perspectives to Halt Cancer Progression.Pharmaceutics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundStimulating inflammatory tumor associated macrophages can overcome resistance to PD-(L)1 blockade. We previously conducted a phase I trial of cabiralizumab (anti-CSF1R), sotigalimab (CD40-agonist) and nivolumab. Our current purpose was to study the activity and cellular effects of this three-drug regimen in anti-PD-1-resistant melanoma.
methodsWe employed a Simon's two-stage design and analyzed circulating immune cells from patients treated with this regimen for treatment-related changes. We assessed various dose levels of anti-CSF1R in murine melanoma models and studied the cellular and molecular effects.
resultsThirteen patients were enrolled in the first stage. We observed one (7.7%) confirmed and one (7.7%) unconfirmed partial response, 5 patients had stable disease (38.5%) and 6 disease progression (42.6%). We elected not to proceed to the second stage. CyTOF analysis revealed a reduction in non-classical monocytes. Patients with prolonged stable disease or partial response who remained on study for longer had increased markers of antigen presentation after treatment compared to patients whose disease progressed rapidly. In a murine model, higher anti-CSF1R doses resulted in increased tumor growth and worse survival. Using single-cell RNA-sequencing, we identified a suppressive monocyte/macrophage population in murine tumors exposed to higher doses.
conclusionsHigher anti-CSF1R doses are inferior to lower doses in a preclinical model, inducing a suppressive macrophage population, and potentially explaining the disappointing results observed in patients. While it is impossible to directly infer human doses from murine studies, careful intra-species evaluation can provide important insight. Cabiralizumab dose optimization is necessary for this patient population with limited treatment options.
trial registrationClinicalTrials.gov Identifier: NCT03502330.
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.