Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors
<p dir="ltr">Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. The recent FDA approval for immune checkpoint inhibition in c...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | |
| منشور في: |
2020
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513512315813888 |
|---|---|
| author | Adviti Naik (673163) |
| author2 | Julie Decock (44558) |
| author2_role | author |
| author_facet | Adviti Naik (673163) Julie Decock (44558) |
| author_role | author |
| dc.creator.none.fl_str_mv | Adviti Naik (673163) Julie Decock (44558) |
| dc.date.none.fl_str_mv | 2020-11-26T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fonc.2020.598626 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Lactate_Metabolism_and_Immune_Modulation_in_Breast_Cancer_A_Focused_Review_on_Triple_Negative_Breast_Tumors/26095096 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Medical biochemistry and metabolomics Oncology and carcinogenesis triple negative breast cancer lactate acidosis immunotherapy tumor metabolism Warburg effect metabolic reprogramming anti-tumor immunity immunosuppression |
| dc.title.none.fl_str_mv | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. The recent FDA approval for immune checkpoint inhibition in combination with nab-paclitaxel for the treatment of metastatic TNBC created opportunity to advocate for immunotherapy in TNBC patients. However, improving the current low response rates is vital. Most cancers, including TNBC tumors, display metabolic plasticity and undergo reprogramming into highly glycolytic tumors through the Warburg effect. Consequently, accumulation of the metabolic byproduct lactate and extracellular acidification is often observed in several solid tumors, thereby exacerbating tumor cell proliferation, metastasis, and angiogenesis. In this review, we focus on the role of lactate acidosis in the microenvironment of glycolytic breast tumors as a major driver for immune evasion with a special emphasis on TNBCs. In particular, we will discuss the role of lactate regulators such as glucose transporters, lactate dehydrogenases, and lactate transporters in modulating immune functionality and checkpoint expression in numerous immune cell types. This review aims to spark discussion on interventions targeting lactate acidosis in combination with immunotherapy to provide an effective means of improving response to immune checkpoint inhibitors in TNBC, in addition to highlighting challenges that may arise from TNBC tumor heterogeneity.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fonc.2020.598626" target="_blank">https://dx.doi.org/10.3389/fonc.2020.598626</a></p><p><br></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_5e7f8f91a1762921d6afc100b56e68b5 |
| identifier_str_mv | 10.3389/fonc.2020.598626 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26095096 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast TumorsAdviti Naik (673163)Julie Decock (44558)Biomedical and clinical sciencesImmunologyMedical biochemistry and metabolomicsOncology and carcinogenesistriple negative breast cancerlactate acidosisimmunotherapytumor metabolismWarburg effectmetabolic reprogramminganti-tumor immunityimmunosuppression<p dir="ltr">Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. The recent FDA approval for immune checkpoint inhibition in combination with nab-paclitaxel for the treatment of metastatic TNBC created opportunity to advocate for immunotherapy in TNBC patients. However, improving the current low response rates is vital. Most cancers, including TNBC tumors, display metabolic plasticity and undergo reprogramming into highly glycolytic tumors through the Warburg effect. Consequently, accumulation of the metabolic byproduct lactate and extracellular acidification is often observed in several solid tumors, thereby exacerbating tumor cell proliferation, metastasis, and angiogenesis. In this review, we focus on the role of lactate acidosis in the microenvironment of glycolytic breast tumors as a major driver for immune evasion with a special emphasis on TNBCs. In particular, we will discuss the role of lactate regulators such as glucose transporters, lactate dehydrogenases, and lactate transporters in modulating immune functionality and checkpoint expression in numerous immune cell types. This review aims to spark discussion on interventions targeting lactate acidosis in combination with immunotherapy to provide an effective means of improving response to immune checkpoint inhibitors in TNBC, in addition to highlighting challenges that may arise from TNBC tumor heterogeneity.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fonc.2020.598626" target="_blank">https://dx.doi.org/10.3389/fonc.2020.598626</a></p><p><br></p>2020-11-26T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fonc.2020.598626https://figshare.com/articles/journal_contribution/Lactate_Metabolism_and_Immune_Modulation_in_Breast_Cancer_A_Focused_Review_on_Triple_Negative_Breast_Tumors/26095096CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260950962020-11-26T09:00:00Z |
| spellingShingle | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors Adviti Naik (673163) Biomedical and clinical sciences Immunology Medical biochemistry and metabolomics Oncology and carcinogenesis triple negative breast cancer lactate acidosis immunotherapy tumor metabolism Warburg effect metabolic reprogramming anti-tumor immunity immunosuppression |
| status_str | publishedVersion |
| title | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| title_full | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| title_fullStr | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| title_full_unstemmed | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| title_short | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| title_sort | Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors |
| topic | Biomedical and clinical sciences Immunology Medical biochemistry and metabolomics Oncology and carcinogenesis triple negative breast cancer lactate acidosis immunotherapy tumor metabolism Warburg effect metabolic reprogramming anti-tumor immunity immunosuppression |