Intratumoral dendritic cell immunotherapy controls dissemination of metastasis-initiating cancer cells, even in patients with metastatic breast cancer

Sep 30, 2026

Metastatic breast cancer patients face few curative options as therapy resistance and ongoing formation of new metastases persist. Dissemination of metastasis-initiating cancer cells (MICs) during disease progression underlies overt metastasis, yet no established therapies directly block MIC dissemination. The study reports preclinical and clinical evidence that intratumoral type I polarized dendritic cell (DC1) immunotherapy limits MIC dissemination, including stage I–III HER2+ disease and a case of de novo stage IV.

LanguageEnglish

CategoryHealthcare

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Open access Case report Intratumoral dendritic cell immunotherapy controls dissemination of metastasis-initiating cancer cells, even in patients with metastatic breast cancer Aixa Soyano ,1 Marie Catherine Lee,1 Hyo S Han,1 Amy Aldrich,2 Hatem Soliman,1 Sy K Olson-Mcpeek,2 Caitlyn N Balsay-Patel,1 Paige Aiello,1 Carly M Farrell,1 Robert Weinfurtner,3 Eliana Burgos,4 Brian J Czerniecki ,1,2 Ganesan Ramamoorthi2 To cite: Soyano A, Lee MC, Han HS, et al. Intratumoral dendritic cell immunotherapy controls dissemination of metastasis-initiating cancer cells, even in patients with metastatic breast cancer. Journal for ImmunoTherapy of Cancer 2026;14:e013590 . doi:10.1136/jitc-2025-013590 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2025-013590](jitc-2025-013590)) . Accepted 23 December 2025 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. 1Department of Breast Oncology, Moffitt Cancer Center, Tampa, Florida, USA 2Clinical Science Division, Moffitt Cancer Center, Tampa, Florida, USA 3Department of Radiology, Moffitt Cancer Center, Tampa, Florida, USA 4Morsani College of Medicine, University of South Florida, Tampa, Florida, USA Correspondence to Dr Brian J Czerniecki; [brian.czerniecki@moffitt.org](brian.czerniecki@moffitt.org) ABSTRACT Patients with metastatic breast cancer (MBC) have limited opportunities for a cure, as they develop resistance to therapies and continually form new metastases. Clinical overt metastases emerge from metastasis-initiating cancer cells (MICs) that disseminate during breast cancer (BC) progression. Currently, there are no available therapies that inhibit MIC dissemination to prevent overt metastasis. We provide preclinical evidence that intratumoral (IT) delivery of type I polarized dendritic cells (DC1) limited the MIC dissemination mechanisms in tumor lesions of human epidermal growth factor receptor 2 (HER2)+ mammary carcinoma. Interferon gamma, a prominent cytokine secreted by T helper 1 and innate-like immune effector cells, inhibited dissemination of MICs from the tumor lesions via the modulation of HER2/progesterone receptor/Wnt family member 4/receptor activator of nuclear factor kappa beta ligand signaling. Importantly, we provide clinical evidence that in patients with stage I–III HER2+ BC, there was significant regression of the primary tumor treated with IT DC1, as well as inhibition of disseminating MIC phenotypes. We observed a reduced burden of MICs in the bone marrow (BM) of patients with stage I–III HER2+BC treated with IT DC1, compared with untreated patients and those treated with standard neoadjuvant HER2 therapies paclitaxel, with or without carboplatin, trastuzumab and pertuzumab (Taxol, Carboplatin, Herceptin and Perjeta or THP) . We also treated a single patient with de novo stage IV HER2+ MBC with trastuzumab, pertuzumab and tamoxifen in combination with IT DC1 . Remarkably, this treatment resulted in nearcomplete regression of primary tumor and metastatic disease, along with inhibition of MIC seeding in the BM. These findings suggest an intriguing strategy to inhibit the dissemination of MICs and prevent further overt metastasis in all patients with BC. INSIGHTS We present clinical evidence that intratumoral type I polarized dendritic cells (DC1) immunotherapy, which is primed to activate CD4Th1 and innate-like immune effector cells, can inhibit dissemination of metastasis-initiating cancer cells (MICs) from the primary tumor lesions. This approach provides a potential strategy to prevent MIC seeding in distant organs and ultimately prevent further overt metastasis in patients with breast cancer. INTRODUCTION Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide, with the

FAQs

What problem does this study address in metastatic breast cancer?

It targets how metastasis-initiating cancer cells disseminate during breast cancer progression, which drives overt metastasis and late recurrence.

How does intratumoral DC1 immunotherapy influence MIC dissemination?

The document reports that intratumoral type I polarized dendritic cells limit MIC dissemination mechanisms in tumor lesions, with interferon gamma contributing via modulation of HER2/PR/Wnt family member 4/RANKL signaling.

What clinical evidence is provided for patients receiving IT DC1?

For stage I–III HER2+ breast cancer, the primary tumors showed significant regression and disseminating MIC phenotypes were inhibited, with reduced MIC burden in bone marrow compared with untreated or standard neoadjuvant HER2 therapies.

Sep 30, 2026

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