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P4. Intratumoral dendritic cell immunotherapy reduces both the dissemination and capacity of metastasis initiating cancer cells to form overt metastasis

Thursday, March 5, 2026
10:53 AM - 11:00 AM MST
Location: 301A
Introduction: Metastasis initiating cancer cells (MICs) are known to drive the outgrowth of overt metastatic disease in breast cancer (BC) patients. There are no proven therapies available that specifically target and inhibit dissemination of MICs and MIC-driven metastasis. Our recent findings demonstrate that tumor antigen targeting type 1 conventional dendritic cells (cDC1) activate immune effector cells to halt MIC dissemination and metastasis in preclinical models. This study aims to evaluate the effects of intratumoral (IT) cDC1 immunotherapy on MIC dissemination and metastasis seeding in BC patients treated with neoadjuvant chemotherapy (NACT).


Methods: Bone marrow (BM) samples were obtained during BC surgery under an ongoing IRB-approved, single-center prospective study. MICs were isolated from the BM using immunomagnetic negative selection and EpCAM-based immunomagnetic enrichment. The MICs were then quantified and confirmed for cancer cell phenotype by flow cytometry, cytopathology and single cell RNA sequencing. Additionally, IT cDC1 immunotherapy- mediated alterations in MIC dissemination in BC patients (pts) was examined. The ability of patient-derived MICs to grow primary tumors and metastasis was evaluated using NSG immunodeficient mouse model.


Results: A total of 62 female pts underwent BM aspiration during BC surgery. The median age was 57 (range 27-83) years old. All pts were treated with standard of care (SOC) NACT. Twenty five of the pts also received IT cDC1 immunotherapy prior to NACT. The mean number of MICs per ml of BM was 48.2 for the cDC1 + SOC group (n=25) vs 162.2 for the SOC only group (n=37). Sixteen (64%) of the cDC1 group had a pathologic complete response (pCR) on final pathology compared to 16 (43.2%) of the SOC only group. Notably, IT cDC1 immunotherapy significantly reduced the disseminating MIC phenotypes (HER2+PR-PCK+ and HER2+PR-WNT4+RANKL+PCK+) in the tumor lesions of HER2+ BC patients. MICs from SOC-treated pts were able to grow primary tumors and metastasis in NSG mice. Strikingly, MICs from pts treated with IT cDC1 immunotherapy failed to grow both primary tumors and metastasis in NSG mice.


Conclusions: IT cDC1 immunotherapy administered prior to chemotherapy attenuated the dissemination of MICs from the tumor lesions of BC pts. It also diminished the MIC burden in the BM and overt metastatic potential of MICs compared to SOC alone. These findings highlight IT DC1 immunotherapy as a promising approach to specifically target and inhibit MICs, thereby reducing recurrence and overt metastasis in BC pts.

Learning Objectives:

  • Describe our technique of identifying and quantifying MICs in bone marrow
  • Discuss the potential of IT cDC1 immunotherapy as a novel strategy to inhibit MIC burden and functionality
  • Evaluate the impact of IT cDC1 immunotherapy on the metastatic potential and tumorigenicity of patient-derived MICs