Cancer-associated adipocytes as immunomodulators in cancer

Wu, Qi; Li, Bei; Li, Juanjuan; Sun, Si; Yuan, Jingping

doi:10.1186/s40364-020-00257-6

Cited by 59 publications

(84 citation statements)

References 213 publications

(304 reference statements)

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“…Indoleamine 2,3‐dioxygenase, an enzyme that mediates the metabolism of tryptophan to kynurenine, is highly expressed in both cancer and immunomodulatory cells. Kynurenine supports intratumoral Treg differentiation and activation of the aryl hydrocarbon receptor, which is involved in T‐cell differentiation into FoxP3‐positive Tregs 42 . High levels of adenosine promote Treg‐mediated suppressive activity through adenosine A2A receptor signaling 43 .…”

Section: The Role Of Tregs In Metabolic Reprogramming Of the Tmementioning

confidence: 99%

Regulatory T cells: Their role in triple‐negative breast cancer progression and metastasis

Malla¹,

Padmaraju²,

Vempati³

et al. 2022

Cancer

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Triple‐negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. This tumorigenicity is independent of hormonal or HER2 pathways because of a lack of respective receptor expression. TNBC is extremely prone to drug resistance and early recurrence because of T‐regulatory cell (Treg) infiltration into the tumor microenvironment (TME) in addition to other mechanisms like genomic instability. Tumor‐infiltrating Tregs interact with both tumor and stromal cells as well as extracellular matrix components in the TME and induce an immune‐suppressive phenotype. Hence, treatment of TNBC with conventional therapies remains challenging. Understanding the protective mechanism of Tregs in shielding TNBC from antitumor immune responses in the TME will pave the way for developing novel, immune‐based therapeutics. The current review focuses on the role of tumor‐infiltrating Tregs in tumor progression and metabolic reprogramming of the TME. The authors have extended their focus to oncotargeting Treg‐mediated immune suppression in breast cancer. Because of its potential role in the TME, modulating Treg activity may provide a novel strategic intervention to combat TNBC. Both under laboratory conditions and in clinical trials, currently available anticancer drugs and natural therapeutics as potential agents for targeting Tregs are explored.

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Section: The Role Of Tregs In Metabolic Reprogramming Of the Tmementioning

confidence: 99%

Regulatory T cells: Their role in triple‐negative breast cancer progression and metastasis

Malla¹,

Padmaraju²,

Vempati³

et al. 2022

Cancer

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“…Apart from PD-1 signaling, other immune checkpoints, abnormal angiogenesis, immunosuppressive immune cells or cytokines, cancer-associated adipocytes, and hyperactive cancer-associated fibroblasts also modulate cancer-immune set point and promote immune tolerance [15][16][17][18][19][20]. Logically, removing these negative factors could enhance the therapeutic effect of α-PD-1/PD-L1 and relieve drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

et al. 2022

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Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.

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“…IL-35 can control the activity of immune cells within the TME, and these cells can, in turn, regulate local IL-35 expression and function (8,15). For example, Tregs and Bregs produce IL-35 to regulate the immune response and to facilitate tumor growth by constraining the activation of innate and adaptive immune cells (26,27). In this review, we explore the association between IL-35 and immune cells in the TME in order to demonstrate the broad applicability of IL-35 in tumor immunology.…”

Section: Introductionmentioning

confidence: 99%

IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

et al. 2021

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Interleukin-35 (IL-35) is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35 that has recently been shown to play diverse and important roles in the tumor microenvironment (TME). Owing to its immunosuppressive activity and ability to promote tumor growth and progression, IL-35 is widely recognized as a key mediator of TME status. Immune cells are key mediators of diverse tumor-related phenotypes, and immunosuppressive cytokines such as IL-35 can promote tumor growth and metastasis in TME. These influences should be considered together. Since tumor immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance, a new target or efficacy enhancing factor is urgently needed. Suppressing IL-35 production and activity has been demonstrated as an effective factor that inhibits tumor cells viability, and further investigation of this cytokine is warranted. However, the mechanistic basis for IL-35-mediated regulation of immune cells in the TME remains to be fully clarified. In the present review, we explore the roles of IL-35 in regulating immune cells within the TME. In addition, we highlight IL-35 as a specific immunological target and discuss its possible relevance in the context of immunotherapy. Lastly, we sought to summarize potential future research directions that may guide the advancement of current understanding regarding the role of this important cytokine as a regulator of oncogenesis.

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Cancer-associated adipocytes as immunomodulators in cancer

Cited by 59 publications

References 213 publications

Regulatory T cells: Their role in triple‐negative breast cancer progression and metastasis

Regulatory T cells: Their role in triple‐negative breast cancer progression and metastasis

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

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