Lactate induced HIF-1α-PRMT1 cross talk affects MHC I expression in monocytes

Gupta, Piyushi; Singh, Ankita; Gowda, Pruthvi; Ghosh, Sadashib; Chatterjee, Arpita; Sen, Ellora

doi:10.1016/j.yexcr.2016.08.008

Cited by 17 publications

(9 citation statements)

References 35 publications

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“…It is well established that acidity, is a major “attractor” of myeloid cells to tumor site, and contributes to alter their anti-tumor response. In fact, a study indicated in prostate cancer, that extracellular tumor acidity (pH 6.8) contributes to carcinogenesis by altering the state of macrophage infiltration, through the modulation of MHC I ( 86 ). In another study, lactic acid was described to induce M2-like polarization of TAMs through HIF-1α, arginase I and VEGF ( 87 ).…”

Section: Role Of Microenvironmental Acidosis In Immune Cellsmentioning

confidence: 99%

Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation

Boussadia¹,

Zanetti²,

Parolini³

2020

Transl Cancer Res TCR

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Tumor microenvironment (TME) is a complex milieu in which tumor grows, develops and progresses through a complex bi-directional cross-talk with immune-, stromal cells, and the extracellular matrix (ECM). In this context, tumor-derived exosomes (TE) drive the fate of tumor cells through a stimulatory or inhibitory role on immune system. In fact, TE can induce the apoptosis of cells of the immune surveillance, and enhance the proliferation and survival of stromal cells that sustain tumor development.However, depending on the molecular cargo, TE are also able to stimulate anti-tumor immune response.TME is mainly characterized by the acidic pH that contributes to tumor development, through multiple mechanisms. Among these, the impairment of tumor immune surveillance does occur within acidic TME, and is directly mediated by acidic pH or by molecular cargo carried by TE. Little is known about the role of TE in immunomodulation in acidic conditions. The present review summarizes the studies describing the role of microenvironmental acidity and TE in immune system modulation.

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Section: Role Of Microenvironmental Acidosis In Immune Cellsmentioning

confidence: 99%

Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation

Boussadia¹,

Zanetti²,

Parolini³

2020

Transl Cancer Res TCR

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“…The same holds for DC maturation markers like CD80, CD83 or CD86, where several studies found no effects [99, 101, 102], but upregulation [100] and downregulation [95–97, 103] were reported as well. Hypoxic alteration of MHC-I expression is less well studied, however HIF-1α activity is implied in upregulating MHC-I expression [104]. These contradicting results likely arise from the complex interplay of ROS and hypoxia signaling with immune cell activation pathways.…”

Section: Introductionmentioning

confidence: 99%

Oxygen in the tumor microenvironment: effects on dendritic cell function

2019

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Solid tumors grow at a high speed leading to insufficient blood supply to tumor cells. This makes the tumor hypoxic, resulting in the Warburg effect and an increased generation of reactive oxygen species (ROS). Hypoxia and ROS affect immune cells in the tumor micro-environment, thereby affecting their immune function. Here, we review the known effects of hypoxia and ROS on the function and physiology of dendritic cells (DCs). DCs can (cross-)present tumor antigen to activate naive T cells, which play a pivotal role in anti-tumor immunity. ROS might enter DCs via aquaporins in the plasma membrane, diffusion across the plasma membrane or via extracellular vesicles (EVs) released by tumor cells. Hypoxia and ROS exert complex effects on DCs, and can both inhibit and activate maturation of immature DCs. Furthermore, ROS transferred by EVs and/or produced by the DC can both promote antigen (cross-)presentation through phagosomal alkalinization, which preserves antigens by inhibiting proteases, and by direct oxidative modification of proteases. Hypoxia leads to a more migratory and inflammatory DC phenotype. Lastly, hypoxia alters DCs to shift the T- cell response towards a tumor suppressive Th17 phenotype. From numerous studies, the concept is emerging that hypoxia and ROS are mutually dependent effectors on DC function in the tumor micro-environment. Understanding their precise roles and interplay is important given that an adaptive immune response is required to clear tumor cells.

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“…Lactic acid derived from tumor cells functions as an immunosuppressive mediator, attenuating the differentiation of and cytokine production by T cells and monocytes in vitro and in vivo 11 , 21 , 27 . The role of lactic acid in macrophage polarization and function has been recently elucidated.…”

Section: Discussionmentioning

confidence: 99%

Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization

Niu

et al. 2021

Cell Death Dis

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Endocrine therapy is the standard treatment for estrogen receptor (ER)-positive breast cancer, but tumors eventually develop resistance. However, endocrine therapy resistance mechanisms mediated through interactions between breast cancer cells and tumor-associated macrophages (TAMs) are still unclear. Here, we characterized sodium/glucose cotransporter 1 (SGLT1) overexpression drives the highly glycolytic phenotype of tamoxifen-resistant breast cancer cells where enhanced lactic acid secretion promotes M2-like TAM polarization via the hypoxia-inducible factor-1α/signal transducer and activator of transcription-3 pathway. In turn, M2-like TAMs activate breast cancer cells through EGFR/PI3K/Akt signaling, providing feedback to upregulate SGLT1 and promote tamoxifen resistance and accelerate tumor growth in vitro and in vivo. Higher expression of SGLT1 and CD163+ TAMs was associated with endocrine-resistant ER-positive breast cancers. Our study identifies a novel vicious cycle of metabolic reprogramming, M2-like TAM polarization, and endocrine therapy resistance, which involves SGLT1, proposing SGLT1 as a therapeutic target to overcome endocrine therapy resistance in breast cancer.

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Lactate induced HIF-1α-PRMT1 cross talk affects MHC I expression in monocytes

Cited by 17 publications

References 35 publications

Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation

Role of microenvironmental acidity and tumor exosomes in cancer immunomodulation

Oxygen in the tumor microenvironment: effects on dendritic cell function

Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization

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