Cited by 305Cancer Immunotherapy and BiomarkersCancer, Hypoxia, and MetabolismBreast Cancer Treatment Studies

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Chemotherapy induces enrichment of CD47 + /CD73 + /PDL1 + immune evasive triple-negative breast cancer cells

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Samanta, Debangshu, Park, Youngrok, Ni, Xuhao, Li, Huili, Zahnow, Cynthia A., Gabrielson, Edward, Pan, Fan, Semenza, Gregg L.·2018·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1718197115PMC PMC5819443

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Abstract

Significance Cytotoxic chemotherapy is frequently used in patients with triple-negative breast cancer (TNBC). Although patients initially respond to the treatment, the cancer often comes back and kills the patient. Recent studies have demonstrated that cancer cells express genes that protect them from killing by immune cells, but the stimulus that prompts this response is unknown. We show that when TNBC cells are treated with chemotherapy, the surviving cells turn on genes that enable them to escape killing by the immune system. We identify hypoxia-inducible factors (HIFs), which are known to promote metastasis of TNBC, as responsible for this countertherapeutic effect. We show that coadministration of an HIF inhibitor with chemotherapy blocks the ability of surviving TNBC cells to evade the immune system.

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RETRACTED: Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells
Samanta, D., Gilkes, D. M., Chaturvedi, P., Xiang, L., & Semenza, G. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421438111 · Cited by 460
Self-citation
Retracted
RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
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Self-citation
Retracted
RETRACTED ARTICLE: HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs
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Additional file 4 of Prognostic stratification based on HIF-1α signaling for evaluating hypoxia status and immune landscape in hepatocellular carcinoma
Zhuang, H., Zhang, Z., Chen, B., Tang, C., Chen, X., Tan, W., Yang, L., Xie, Z., Ma, X., Wang, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26590802
Additional file 3 of Prognostic stratification based on HIF-1α signaling for evaluating hypoxia status and immune landscape in hepatocellular carcinoma
Zhuang, H., Zhang, Z., Chen, B., Tang, C., Chen, X., Tan, W., Yang, L., Xie, Z., Ma, X., Wang, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26590799
Additional file 5 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627149
Additional file 5 of Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program
Ramírez, J. S., Díaz, Y. M., Béquet‐Romero, M., Hernández-Bernal, F., Martín‐Bauta, Y., Selman-Housein Bernal, K.-H., de la Torre Santos, A. V., de la Iglesia, M. P., Trimiño-Lorenzo, L., & Ayala Avila, M. (2020) · Figshare · doi:10.6084/m9.figshare.11986119
Additional file 4 of Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program
Ramírez, J. S., Díaz, Y. M., Béquet‐Romero, M., Hernández-Bernal, F., Martín‐Bauta, Y., Selman-Housein Bernal, K.-H., de la Torre Santos, A. V., de la Iglesia, M. P., Trimiño-Lorenzo, L., & Ayala Avila, M. (2020) · Figshare · doi:10.6084/m9.figshare.11986116
Additional file 2 of Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program
Ramírez, J. S., Díaz, Y. M., Béquet‐Romero, M., Hernández-Bernal, F., Martín‐Bauta, Y., Selman-Housein Bernal, K.-H., de la Torre Santos, A. V., de la Iglesia, M. P., Trimiño-Lorenzo, L., & Ayala Avila, M. (2020) · Figshare · doi:10.6084/m9.figshare.11986104
Additional file 2 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627140
Additional file 3 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627143
Additional file 6 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627152
Additional file 8 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627158
Additional file 1 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627137
Additional file 7 of Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer
Ji, S., Yu, H., Zhou, D., Fan, X., Duan, Y., Tan, Y., Lang, M., & 邵国利 (2024) · Figshare · doi:10.6084/m9.figshare.26627155
Additional file 2 of Prognostic stratification based on HIF-1α signaling for evaluating hypoxia status and immune landscape in hepatocellular carcinoma
Zhuang, H., Zhang, Z., Chen, B., Tang, C., Chen, X., Tan, W., Yang, L., Xie, Z., Ma, X., Wang, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26590796
Additional file 3 of Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program
Ramírez, J. S., Díaz, Y. M., Béquet‐Romero, M., Hernández-Bernal, F., Martín‐Bauta, Y., Selman-Housein Bernal, K.-H., de la Torre Santos, A. V., de la Iglesia, M. P., Trimiño-Lorenzo, L., & Ayala Avila, M. (2020) · Figshare · doi:10.6084/m9.figshare.11986113
Additional file 1 of Prognostic stratification based on HIF-1α signaling for evaluating hypoxia status and immune landscape in hepatocellular carcinoma
Zhuang, H., Zhang, Z., Chen, B., Tang, C., Chen, X., Tan, W., Yang, L., Xie, Z., Ma, X., Wang, Q., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26590793

Authors: Samanta, D., Park, Y., Ni, X., Li, H., Zahnow, C. A., Gabrielson, E., Pan, F., & Semenza, G. L.
Affiliations: Johns Hopkins University (US)
Corresponding author: Semenza, Gregg L.
ORCID: Ni, Xuhao
Li, Huili
Zahnow, Cynthia A.
Gabrielson, Edward
Pan, Fan
Semenza, Gregg L.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2018-01-24
Volume: 115
Issue: 6
Pages: E1239-E1248
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1718197115
PMC: PMC5819443
OpenAlex: W2785041354
Cited by: 302
References: 63
Citations by year: 2026: 13 · 2025: 19 · 2024: 35 · 2023: 47 · 2022: 53 · 2021: 45 · 2020: 43 · 2019: 28 · 2018: 17
FWCI: 12.50
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 181 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Emerson Collective Cancer Research Fund (n/a)
American Cancer Society (RP-16-239-06-COUN)
Cindy Rosencrans Fund for Triple Negative Breast Cancer (n/a)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: triple-negative breast cancer, chemoresistance, immune evasion, CD47, CD73, PD-L1, hypoxia-inducible factor, HIF inhibitors, tumor immune evasion, tumor cell survival
MeSH terms: Animals, Antineoplastic Agents, Female, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, T-Lymphocytes, Tumor Cells, Cultured, 5'-Nucleotidase, Gene Expression Regulation, Neoplastic, Apoptosis, Tumor Escape, Xenograft Model Antitumor Assays, Mice, Hypoxia-Inducible Factor 1, CD47 Antigen, GPI-Linked Proteins, B7-H1 Antigen, Triple Negative Breast Neoplasms

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Chemotherapy induces enrichment of CD47 + /CD73 + /PDL1 + immune evasive triple-negative breast cancer cells

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