ArticleJournal for immunotherapy of cancer2024
Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast 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. It is linked to trial NCT04081389 (Phase I Clinical Trial Assessing the Combination of Chemokine Modulation With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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.
Phase I Clinical Trial Assessing the Combination of Chemokine Modulation With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The impact of intratumor heterogeneity on outcome and resistance to therapy in primary breast cancer: a systematic review.Medical oncology (Northwood, London, England) · 2026Pooled it
- The tumor microenvironment in triple negative breast cancer and a strategy to improve responses to immunotherapy using cryoablation and immunostimulants.Cancer biology & therapy · 2026Review
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- PGE2-mediated NK cell reprogramming drives acquired immunotherapy resistance in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Targeting MORC2 activates transposable element-mediated viral mimicry and potentiates immune checkpoint blockade in triple-negative breast cancer.Molecular cancer · 2026Article
- Synergy between TLR3-ligand and IFN-α in the transient sensitization of "Cold" tumors to PD-1 blockade and the induction of systemic immunity.Journal for immunotherapy of cancer · 2025Article
- Paclitaxel, interferons and functional reprogramming of tumor-associated macrophages in optimized chemo-immunotherapy.Journal for immunotherapy of cancer · 2025Review
- Meeting Highlights The 4th Marie Skłodowska-Curie Symposium on cancer research and care: Mechanisms of support for regional & international collaborations.Wiadomosci lekarskie (Warsaw, Poland : 1960) · 2025Article
- IFNγ-mediated suppression of alternative NF-κB in tumor-resident myeloid cells promotes selective recruitment of cytotoxic but not regulatory T cells.Frontiers in immunology · 2025Article
- Celecoxib in oncology: targeting the COX-2/PGEFrontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
backgroundHigher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR to NAC is achieved only in 30-40% of patients. The combination of NAC with pembrolizumab increases the pCR rate but at the cost of immune-related adverse events (irAEs). Based on these considerations, we tested if systemic infusion of the chemokine modulatory regimen (CKM; selective toll-like receptor 3 (TLR3) agonist rintatolimod, interferon (IFN)-α2b, and cyclooxygenase-2 (COX-2) inhibitor celecoxib) regimen can be safely combined with NAC to enhance intratumoral CTL numbers and NAC effectiveness.
methodsPhase I study NCT04081389 evaluated nine patients with early-stage TNBC who received 3 weeks of paclitaxel with CKM (dose-escalation of IFN-α2b), followed by 9 weeks of paclitaxel alone, dose-dense doxorubicin and cyclophosphamide, and surgery. Primary and secondary endpoints were safety and clinical efficacy, respectively.
resultsThe combination treatment was well-tolerated with no dose-limiting toxicities or irAEs. 5/9 patients achieved pCR and one patient had microinvasive disease (ypTmic). We observed elevated IFN signature and uniform decreases in CTL numbers (average 8.3-fold) in the blood of all treated patients. This was accompanied by reciprocal uniform increases in CD8β (overall 5.9-fold), CD8α/FoxP3 (2.11-fold), and CCL5 (4.73-fold) transcripts in TME, particularly pronounced in patients with pCR. Multiplex immunohistochemistry revealed selectively increased numbers of CTL (but not regulatory T cells) in both the epithelial and stromal tumor compartments and early decreases in the numbers of αSMA
conclusionsCombined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab.
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