The Role of Regulatory T Cells in Cancer Treatment Resistance

Dąbrowska, Anna; Grubba, Magdalena; Balihodzic, Amar; Szot, Olga; Sobocki, Bartosz Kamil; Perdyan, Adrian

doi:10.3390/ijms241814114

Cited by 3 publications

(6 citation statements)

References 74 publications

(108 reference statements)

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“…Targeting Tregs also has potential applications in cancer treatment. The goal of targeting Tregs for cancer treatment is to enhance the tumor immune response and suppress tumor growth by modulating the activity of the immune system ( 221 ). Immune checkpoint inhibitors have become an important strategy in cancer treatment ( 222 ).…”

Section: Potential Of Treg-based Immunotherapymentioning

confidence: 99%

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

Zong,

Deng,

Chong

2024

Front. Immunol.

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CD4+CD25+Foxp3+ regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining immune homeostasis and preventing excessive immune responses. This review explores the signaling pathways of the cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, and IL-35, which foster the differentiation and enhance the immunosuppressive capabilities of Tregs. It also examines how, conversely, signals mediated by IL-6 and tumor necrosis factor -alpha (TNF-α) can undermine Treg suppressive functions or even drive their reprogramming into effector T cells. The B7 family comprises indispensable co-stimulators for T cell activation. Among its members, this review focuses on the capacity of CTLA-4 and PD-1 to regulate the differentiation, function, and survival of Tregs. As Tregs play an essential role in maintaining immune homeostasis, their dysfunction contributes to the pathogenesis of autoimmune diseases. This review delves into the potential of employing Treg-based immunotherapy for the treatment of autoimmune diseases, transplant rejection, and cancer. By shedding light on these topics, this article aims to enhance our understanding of the regulation of Tregs by cytokines and their therapeutic potential for various pathological conditions.

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Section: Potential Of Treg-based Immunotherapymentioning

confidence: 99%

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

Zong,

Deng,

Chong

2024

Front. Immunol.

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“…Tregs play a critical function within the TME, sustaining immune homeostasis and mitigating excessive inflammation by inhibiting immune responses directed towards self-antigens [ 80 ]. This regulatory function extends also to situations such as autoimmunity and allograft rejection [ 81 ].…”

Section: A More In-depth Insight Into the Role Of Apoptosis In The Im...mentioning

confidence: 99%

“…Tregs contribute to T-cell exhaustion, inhibiting anti-tumor responses through various mechanisms, including APC inhibition, cytokine depletion, and production of immunosuppressive factors, ultimately promoting tumor proliferation, and reducing responses to immunotherapies [ 82 ]. Although Forkhead box protein P3 (FOXP3) serves as a crucial regulator in both the development and suppressive function of CD4 + Tregs, a complicated categorization involves subtypes such as CD4 + CD25 + FOXP3 + , CD4 + CD25 − FOXP3low, CD4 + CD25highCD125low, CD4 + CD25highCD45ROhigh, and CD4 + CD25 + CD62LlowCD44high [ 80 ]. Unlike the well-established biology of CD4 + Tregs, the heterogeneous features of CD8 + Tregs are still being revealed and involve the TGF-β-dependent expression of CD103 and FOXP3 in aggressive tumors [ 83 ].…”

Section: A More In-depth Insight Into the Role Of Apoptosis In The Im...mentioning

confidence: 99%

“…Hypoxia, a key feature of the TME, plays a crucial role in tumor immune evasion, impacting T-cell survival and promoting Treg development and recruitment to the TME via the VEGFR2/VEGF axis [ 80 ]. Tregs, in turn, promote effector T-cell apoptosis by means of granzyme B and hinder their proliferation by consuming IL-2 [ 109 ].…”

Section: A More In-depth Insight Into the Role Of Apoptosis In The Im...mentioning

confidence: 99%

“…Hypoxia indirectly induces effector T-cell apoptosis, also promoting Treg activity, a process counteracted by VEGF inhibition [ 80 ]. Several receptor kinase inhibitors and mAbs have been developed and are currently employed or undergoing clinical trials [ 215 ].…”

Section: Apoptosis Control To Bypass Immunotherapy Resistancementioning

confidence: 99%

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Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Franzese,

Ancona,

Bianchi

et al. 2024

Cells

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Induction of apoptosis represents a promising therapeutic approach to drive tumor cells to death. However, this poses challenges due to the intricate nature of cancer biology and the mechanisms employed by cancer cells to survive and escape immune surveillance. Furthermore, molecules released from apoptotic cells and phagocytes in the tumor microenvironment (TME) can facilitate cancer progression and immune evasion. Apoptosis is also a pivotal mechanism in modulating the strength and duration of anti-tumor T-cell responses. Combined strategies including molecular targeting of apoptosis, promoting immunogenic cell death, modulating immunosuppressive cells, and affecting energy pathways can potentially overcome resistance and enhance therapeutic outcomes. Thus, an effective approach for targeting apoptosis within the TME should delicately balance the selective induction of apoptosis in tumor cells, while safeguarding survival, metabolic changes, and functionality of T cells targeting crucial molecular pathways involved in T-cell apoptosis regulation. Enhancing the persistence and effectiveness of T cells may bolster a more resilient and enduring anti-tumor immune response, ultimately advancing therapeutic outcomes in cancer treatment. This review delves into the pivotal topics of this multifaceted issue and suggests drugs and druggable targets for possible combined therapies.

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Targeting Macrophages as a Novel Therapy to Treat Triple-Negative Breast Cancer: A Literature Review

Todrick,

Ma,

Singh

2024

URNCST Journal

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Triple-negative breast cancer (TNBC) is a highly aggressive form of cancer which lacks the traditional cellular targets of other types of breast cancer. As such, it is increasingly important to find alternative targets to treat this deadly disease. Recently, tumour-associated macrophages (TAMs) have become an exciting area of focus for cancer research and may provide a source of treatment options for TNBC. Macrophages are an important part of the innate immune response and also play a crucial role in tumour progression, inflammation, and metastasis. TAMs fall along a spectrum and are generally presented as either M1 type or M2 type. M1 macrophages are considered anti-tumorigenic whereas M2 macrophages are considered pro-tumorigenic, promoting tumour growth and inhibiting T-cell response. A search of the University of Alberta's online library database was carried out with a specific emphasis on clinical research. Search efforts focused on the effects of macrophages on the progression of breast cancer. Further searches were performed to determine the efficacy of targeting macrophages to treat cancer. Increasing the relative ratio of M1 to M2 macrophages or depletion of macrophages may lead to a better prognosis in TNBC. TAMs may be repolarized to M1 phenotype using metformin, inhibition of SerpinE2, YAP/STAT3, or MED1/PPAR𝛾. Macrophage recruitment to the tumour microenvironment may be inhibited by targeting chemokines such as CCL2. Current methods could not efficiently deplete macrophages at such a high abundance. The abundance of macrophages and their phagocytic properties could instead be exploited to increase tumour cell phagocytosis by targeting the CD47-SIRPɑ axis. Exciting opportunities have been revealed regarding inhibition of macrophage recruitment, repolarization of M2 to M1 type, and through exploitation of phagocytic properties of macrophages. However, conflicting results can be found for all these emerging treatment strategies. Worsening matters is the lack of knowledge regarding macrophage functions and the confusing landscape of macrophages current naming conventions. As such, further research is required to determine the efficacy of macrophages as a target in breast cancer treatment.

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The Role of Regulatory T Cells in Cancer Treatment Resistance

Cited by 3 publications

References 74 publications

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

Apoptosis, a Metabolic “Head-to-Head” between Tumor and T Cells: Implications for Immunotherapy

Targeting Macrophages as a Novel Therapy to Treat Triple-Negative Breast Cancer: A Literature Review

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