Immune checkpoint blockade in triple negative breast cancer influenced by B cells through myeloid-derived suppressor cells
Autor: | Danielle Harrington, Yonghong Wan, Alyssa Vito, Ana L. Portillo, Nader El-Sayes, Samuel T Workenhe, Ian P. MacFawn, Karen L. Mossman, Omar Salem, Ali A. Ashkar, Tullia C. Bruno, Brad H. Nelson, Katy Milne |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer therapy QH301-705.5 medicine.medical_treatment Population Medicine (miscellaneous) Triple Negative Breast Neoplasms Kaplan-Meier Estimate General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Lymphocytes Tumor-Infiltrating Low-dose chemotherapy Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Chlorocebus aethiops medicine Animals Humans Biology (General) education Immune Checkpoint Inhibitors Vero Cells Triple-negative breast cancer Oncolytic Virotherapy education.field_of_study B-Lymphocytes business.industry Myeloid-Derived Suppressor Cells Immunotherapy Combined Modality Therapy Immune checkpoint Blockade Oncolytic virus Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis Myeloid-derived Suppressor Cell Cancer research Female General Agricultural and Biological Sciences business |
Zdroj: | Communications Biology Communications Biology, Vol 4, Iss 1, Pp 1-19 (2021) |
ISSN: | 2399-3642 |
Popis: | Triple negative breast cancer holds a dismal clinical outcome and as such, patients routinely undergo aggressive, highly toxic treatment regimens. Clinical trials for TNBC employing immune checkpoint blockade in combination with chemotherapy show modest prognostic benefit, but the percentage of patients that respond to treatment is low, and patients often succumb to relapsed disease. Here, we show that a combination immunotherapy platform utilizing low dose chemotherapy (FEC) combined with oncolytic virotherapy (oHSV-1) increases tumor-infiltrating lymphocytes, in otherwise immune-bare tumors, allowing 60% of mice to achieve durable tumor regression when treated with immune checkpoint blockade. Whole-tumor RNA sequencing of mice treated with FEC + oHSV-1 shows an upregulation of B cell receptor signaling pathways and depletion of B cells prior to the start of treatment in mice results in complete loss of therapeutic efficacy and expansion of myeloid-derived suppressor cells. Additionally, RNA sequencing data shows that FEC + oHSV-1 suppresses genes associated with myeloid-derived suppressor cells, a key population of cells that drive immune escape and mediate therapeutic resistance. These findings highlight the importance of tumor-infiltrating B cells as drivers of antitumor immunity and their potential role in the regulation of myeloid-derived suppressor cells. Vito et al. investigated the effects of combination therapy in a TNBC tumor model and reported increased tumor-infiltrating lymphocytes that contributed to an improved response to immune checkpoint blockade. By depletion of circulating B cells prior to therapy, the authors showed a loss of therapeutic efficacy and simultaneous expansion of myeloid-derived suppressor cells. |
Databáze: | OpenAIRE |
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