The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Alam, Md Rakibul; Rahman, Md. Mizanur; Li, Zhiguo

doi:10.1016/j.gendis.2023.01.026

Cited by 8 publications

(6 citation statements)

References 151 publications

(210 reference statements)

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“…Patients with low circadian rhythm circadian rhythm signature (CRS) may have a higher TMB and are more likely to benefit from immune checkpoint blocking (ICB) therapy 46 . In the GO pathway enriched by KCNQ4, a large number of studies have shown that the transmembrane transport and concentration of ion channels as transmembrane proteins are also closely related to cancer 47 – 51 .Recent studies have found that plasma membrane disturbance and tumor cell lysis can be an integral part of multimodal therapy strategies for cancer patients through oncolytic polymers as new targets and killing mechanisms 52 . The glycoprotein interaction on the cell surface can participate in immune escape 53 .Inositol 1, 4, 5-triphosphate (IP3Rs) acts as a channel for intracellular calcium (Ca) 2 + to release cellular bioenergetics and participates in cell proliferation and death in cancer 53 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive pan‑cancer analysis of potassium voltage-gated channel Q4 (KCNQ4) gene across multiple human malignant tumors

Zhao,

Li,

Zhang

2023

Sci Rep

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A large number of studies indicate that Potassium Voltage-Gated Channel Q4 (KCNQ4) gene is the cause of non-syndromic hearing loss, but there are few studies investigating the role of KCNQ4 in cancers and scarcity of comprehensive analysis of its involvement in the diagnosis, methylation, mutation, prognosis of various cancer types. Therefore, the aim of this study is to examine the anticancerous and immune effects of KCNQ4 in various cancers and its potential value in breast cancer. In this study, we explored the potential role of KCNQ4 in cancers using public databases and the R software for bioinformatics analysis. The results showed that the low expression of KCNQ4 across specific cancer types was positively associated with low mutation frequency and methylation, and the improved survival. Eight small molecule compounds were identified that could potentially target KCNQ4. In addition, immunohistochemistry confirmed that the KCNQ4 expression was low in breast cancer. In vitro experiments confirmed that overexpression of KCNQ4 inhibited cell migration and invasion and promoted apoptosis. In summary, our comprehensive pan-cancer analysis highlights the potential of KCNQ4 as a cancer marker, and can be used as an auxiliary prognostic indicator and an indicator for immunotherapy in certain tumor types.

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Section: Discussionmentioning

confidence: 99%

Comprehensive pan‑cancer analysis of potassium voltage-gated channel Q4 (KCNQ4) gene across multiple human malignant tumors

Zhao,

Li,

Zhang

2023

Sci Rep

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“…Calcium signaling is involved in exosome biogenesis and secretion. Accordingly, targeting calcium signaling can inhibit the expression of exoPD-L1 ( 71 ). Under hypoxic condition, hypoxia increases production of exoPD-L1 in a hypoxia-inducible factors (HIF)-STAT3-dependent manner ( 71 ).…”

Section: Action Mechanisms and Regulation Of Exopd-l1mentioning

confidence: 99%

“…Accordingly, targeting calcium signaling can inhibit the expression of exoPD-L1 ( 71 ). Under hypoxic condition, hypoxia increases production of exoPD-L1 in a hypoxia-inducible factors (HIF)-STAT3-dependent manner ( 71 ). Therapeutic interventions such as chemotherapeutic agent 5-fluorouracil (5-FU) can promote exoPD-L1 biogenesis and secretion in advanced GC ( 56 ).…”

Section: Action Mechanisms and Regulation Of Exopd-l1mentioning

confidence: 99%

Exosomal PD-L1 in cancer and other fields: recent advances and perspectives

Lu,

Yang

2024

Front. Immunol.

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PD-1/PD-L1 signaling is a key factor of local immunosuppression in the tumor microenvironment. Immune checkpoint inhibitors targeting PD-1/PD-L1 signaling have achieved tremendous success in clinic. However, several types of cancer are particularly refractory to the anti–PD-1/PD-L1 treatment. Recently, a series of studies reported that IFN-γ can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1), which possesses the ability to suppress anticancer immune responses and is associated with anti-PD-1 response. In this review, we introduce the PD-1/PD-L1 signaling, including the so-called ‘reverse signaling’. Furthermore, we summarize the immune treatments of cancers and pay more attention to immune checkpoint inhibitors targeting PD-1/PD-L1 signaling. Additionally, we review the action mechanisms and regulation of exoPD-L1. We also introduce the function of exoPD-L1 as biomarkers. Finally, we review the methods for analyzing and quantifying exoPD-L1, the therapeutic strategies targeting exoPD-L1 to enhance immunotherapy and the roles of exoPD-L1 beyond cancer. This comprehensive review delves into recent advances of exoPD-L1 and all these findings suggest that exoPD-L1 plays an important role in both cancer and other fields.

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“…Program death ligand 1 (PDL-1), an immune suppressive molecule that binds to receptor program death protein 1 (PD-1) and promotes tumour progression by evading immune response, is present in exosomes produced from cancer cells. Ca 2+ signalling is known to control both the generation and secretion of exosomes produced from cancer cells [ 52 ] by influencing the Rab GTPase family and membrane fusion factors [ 53 ] . Preclinical studies with CT26 tumour-bearing mice have mentioned that blocking Ca 2+ channels using dimethyl amiloride (DMA) inhibits exosome release [ 54 ] .…”

Section: Ca 2+ Signalling Via Ca 2+ ...mentioning

confidence: 99%

“…Combining anti-PDL-1 antibody therapy with exosome secretion inhibition using Ca 2+ channel blockers (CCBs) may enhance efficacy. Exosome PDL-1 represents a prominent therapeutic target in immunotherapy resistance [ 52 ] .…”

Section: Ca 2+ Signalling Via Ca 2+ ...mentioning

confidence: 99%

Dysregulation of calcium homeostasis in cancer and its role in chemoresistance

Kumari,

Pullaguri,

Rath

et al. 2024

Cancer Drug Resist

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Globally, cancer, as a major public health concern, poses a severe threat to people’s well-being. Advanced and specialized therapies can now cure the majority of people with early-stage cancer. However, emerging resistance to traditional and novel chemotherapeutic drugs remains a serious issue in clinical medicine. Chemoresistance often leads to cancer recurrence, metastasis, and increased mortality, accounting for 90% of chemotherapy failures. Thus, it is important to understand the molecular mechanisms of chemoresistance and find novel therapeutic approaches for cancer treatment. Among the several factors responsible for chemoresistance, calcium (Ca2+) dysregulation plays a significant role in cancer progression and chemoresistance. Therefore, targeting this derailed Ca2+ signalling for cancer therapy has become an emerging research area. Of note, the Ca2+ signal and its proteins are a multifaceted and potent tool by which cells achieve specific outcomes. Depending on cell survival needs, Ca2+ is either upregulated or downregulated in both chemosensitive and chemoresistant cancer cells. Consequently, the appropriate treatment should be selected based on Ca2+ signalling dysregulation. This review discusses the role of Ca2+ in cancer cells and the targeting of Ca2+ channels, pumps, and exchangers. Furthermore, we have emphasised the role of Ca2+ in chemoresistance and therapeutic strategies. In conclusion, targeting Ca2+ signalling is a multifaceted process. Methods such as site-specific drug delivery, target-based drug-designing, and targeting two or more Ca2+ proteins simultaneously may be explored; however, further clinical studies are essential to validate Ca2+ blockers’ anti-cancer efficacy.

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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Cited by 8 publications

References 151 publications

Comprehensive pan‑cancer analysis of potassium voltage-gated channel Q4 (KCNQ4) gene across multiple human malignant tumors

Comprehensive pan‑cancer analysis of potassium voltage-gated channel Q4 (KCNQ4) gene across multiple human malignant tumors

Exosomal PD-L1 in cancer and other fields: recent advances and perspectives

Dysregulation of calcium homeostasis in cancer and its role in chemoresistance

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