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Article

Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer

McMaster Immunology Research Centre, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
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Author to whom correspondence should be addressed.
Academic Editors: Patrizia Limonta and Fabrizio Fontana
Cancers 2021, 13(21), 5590; https://doi.org/10.3390/cancers13215590
Received: 2 September 2021 / Revised: 27 October 2021 / Accepted: 5 November 2021 / Published: 8 November 2021
We have previously reported that a combination of clinical chemotherapies and oncolytic HSV-1 works to sensitize tumors to respond to immune checkpoint blockade. We further showed that this therapeutic platform worked via the upregulation of B cells and the concomitant control of immunosuppressive myeloid cells. In this manuscript, we sought to further dissect the mechanism of myeloid cell regulation and differentiation and to identify a therapeutically driven gene signature that is associated with the switch in the myeloid phenotype. This work not only impacts triple-negative breast cancer but all solid tumor phenotypes as we aim to better understand the underlying immunology associated with responses to immune checkpoint therapies in these typically refractory disease types.
The era of immunotherapy has seen an insurgence of novel therapies driving oncologic research and the clinical management of the disease. We have previously reported that a combination of chemotherapy (FEC) and oncolytic virotherapy (oHSV-1) can be used to sensitize otherwise non-responsive tumors to immune checkpoint blockade and that tumor-infiltrating B cells are required for the efficacy of our therapeutic regimen in a murine model of triple-negative breast cancer. In the studies herein, we have performed gene expression profiling using microarray analyses and have investigated the differential gene expression between tumors treated with FEC + oHSV-1 versus untreated tumors. In this work, we uncovered a therapeutically driven switch of the myeloid phenotype and a gene signature driving increased tumor cell killing. View Full-Text
Keywords: triple-negative breast cancer; breast cancer; immunotherapy; B cells; myeloid cells; tumor microenvironment; oncolytic virotherapy; chemotherapy triple-negative breast cancer; breast cancer; immunotherapy; B cells; myeloid cells; tumor microenvironment; oncolytic virotherapy; chemotherapy
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MDPI and ACS Style

Vito, A.; El-Sayes, N.; Salem, O.; Wan, Y.; Mossman, K.L. Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer. Cancers 2021, 13, 5590. https://doi.org/10.3390/cancers13215590

AMA Style

Vito A, El-Sayes N, Salem O, Wan Y, Mossman KL. Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer. Cancers. 2021; 13(21):5590. https://doi.org/10.3390/cancers13215590

Chicago/Turabian Style

Vito, Alyssa, Nader El-Sayes, Omar Salem, Yonghong Wan, and Karen L. Mossman. 2021. "Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer" Cancers 13, no. 21: 5590. https://doi.org/10.3390/cancers13215590

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