The Dual Role of Treg in Cancer

Frydrychowicz, Magdalena; Boruczkowski, Maciej; Kolecka-Bednarczyk, Agata; Dworacki, Grzegorz

doi:10.1111/sji.12615

Cited by 79 publications

(77 citation statements)

References 103 publications

(139 reference statements)

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“…Although large numbers of tumor-specific T cells can be generated in patients by active immunization or adoptive transfer, these T cells do not readily translate to tumor cell killing in situ. In fact, the Treg subpopulation of T cells plays an important role in suppressing tumor-specific immunity [29,30]. Thus, our observations ( Figure S8) employing FD/LC analyses of clinical samples from patients with MT KRAS NSCLC had a higher percentage of FOXP3 + Treg-like cells underscore the significance of the present study.…”

Section: Discussionsupporting

confidence: 67%

Phenotypic Switching of Naïve T cells to Immune-suppressive Treg-like Cells by Mutant KRAS

Kalvala

Wallet

Yang

et al. 2019

Preprint

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Oncogenic (mutant) Ras protein Kirsten rat sarcoma viral oncogene homolog (KRAS) promotes uncontrolled proliferation, altered metabolism, and loss of genome integrity in a cell-intrinsic manner. Here, we demonstrate that CD4 + T cells when incubated with tumor-derived exosomes from mutant (MT) KRAS non-small cell lung cancer (NSCLC) cells, patient sera, or a mouse xenograft model, induce phenotypic conversion to FOXP3 + Treg-like cells that are immune-suppressive. Furthermore, transfecting T cells with MT KRAS cDNA alone induced phenotypic switching and mathematical modeling supported this conclusion. Single-cell sequencing identified the interferon pathway as the mechanism underlying the phenotypic switch. These observations highlight a novel cytokineindependent, cell-extrinsic role for KRAS in T cell phenotypic switching. Thus, targeting this new class of Tregs represents a unique therapeutic approach for NSCLC. Since KRAS is the most frequently mutated oncogene in a wide variety of cancers, the findings of this investigation are likely to be of broad interest and have a large scientific impact.

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Section: Discussionsupporting

confidence: 67%

Phenotypic Switching of Naïve T cells to Immune-suppressive Treg-like Cells by Mutant KRAS

Kalvala

Wallet

Yang

et al. 2019

Preprint

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“…Conversely, M2 cells, suppressor cell populations such as Tregs and myeloid‐derived suppressor cells (MDSC) and Th2 cells exhibit tumour‐enabling effects and are associated with poor prognosis . Albeit, recent evidence suggests that the distinction between protumour and antitumour immune populations might be less distinct than anticipated, which is exemplified by association of Tregs with favourable prognosis in some lymphomas and some of the inflammation‐related cancers such as colon cancer . A complete antitumorigenic immune profile would likely to be cancer‐type specific and would only be completed when we identify all the subsets of immune cells and markers for those cells.…”

Section: Duality Of Cancer‐immune System Interactionmentioning

confidence: 99%

“…3,24 Albeit, recent evidence suggests that the distinction between protumour and antitumour immune populations might be less distinct than anticipated, which is exemplified by association of Tregs with favourable prognosis in some lymphomas and some of the inflammation-related cancers such as colon cancer. 25,26 A complete antitumorigenic immune profile would likely to be cancer-type specific and would only be completed when we identify all the subsets of immune cells and markers for those cells. One of the immune components that we do not have a very good picture of its role in tumour settings is complement.…”

Section: System Interactionmentioning

confidence: 99%

Complement system's role in cancer and its therapeutic potential in ovarian cancer

Bareke

Akbuğa

2018

Scand J Immunol

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Cancer immunotherapy is a strong candidate for the long-awaited new edition to standard cancer therapies. For an effective immunotherapy, it is imperative to delineate the players of antitumour immune response. As an important innate immune system effector mechanism, complement is highly likely to play a substantial role in cancer immunity. Studies suggest that there may be two different "states of complement" that show opposing effects on cancer cells; a complement profile that has antitumour effects with low expression of membrane-bound complement regulator proteins (mCRPs), lytic membrane attack complex (MAC) concentration and moderate C5a concentration, and a complement profile that has protumour effects with high expression of mCRPs, sublytic MAC and high concentrations of C5a. One of the cancers that urgently require innovative therapeutic approaches is ovarian cancer, and complement has a potential to be a good target for this purpose. A combinatorial approach where the complement cascade is fine-tuned by inhibiting some of its activities while promoting the others can prove to be a fruitful approach. Herein, we will briefly discuss the cancer-immune system interaction and then present a discussion of complement system's role in tumour immunity and its therapeutic potential for ovarian cancer immunotherapy.

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“…Tregs can suppress the activation, proliferation and cytokine production of immune cells, including CD4+ and CD8+ lymphocytes, B cells, natural killer cells, NKT cells, monocytes, macrophages, antigen‐presenting cells and dendritic cells. There are evidences for either contact‐dependent suppression or suppression via immunosuppressive cytokines, namely interleukin (IL)‐10 and transforming growth factor (TGF)‐ß …”

Section: Introductionmentioning

confidence: 99%

“…There are evidences for either contact-dependent suppression or suppression via immunosuppressive cytokines, namely interleukin (IL)-10 and transforming growth factor (TGF)-ß. [10][11][12] Besides distinct mechanisms of action and production of cytokines, Tregs can be subdivided on the basis of different expression of cell surface markers. 13 Among the reported combinations of cell surface markers, CD3, CD4, CD25 and human transcription factor forkhead box P3 (FoxP3) are considered as the minimally required markers to differentiate Tregs.…”

Section: Introductionmentioning

confidence: 99%

Frequency of circulating subpopulations of T‐regulatory cells in patients with hidradenitis suppurativa

Hessam

Gambichler

Höxtermann

et al. 2019

Acad Dermatol Venereol

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Background Decreased number of T‐regulatory cells (Tregs) and/or their loss of function potentially lead to uncontrolled immune‐mediated inflammatory responses. There are only few data available on Tregs in hidradenitis suppurativa (HS) – a disease in which it has been suggested that host immune factors and an overactive immune system of the follicular epithelium play a pathogenetic role. Objectives To analyse frequencies of Tregs subpopulations in blood of HS patients in comparison with a healthy control group. Materials & methods Blood samples obtained from HS patients and healthy controls were evaluated by flow cytometry and enzyme‐linked immunosorbent assay. Results The frequency of natural Tregs among CD4+ T lymphocytes were significantly reduced in the HS group compared to the healthy controls. The proportion of activated Tregs, non‐suppressive Tregs and proliferating Tregs showed no significant difference when compared to controls. Regarding Tregs frequencies, there was no significant difference between the three Hurley stages. Serum concentrations of IL‐10, TGF‐ß1 and IL‐17A did not show significant differences between the HS and control group. Conclusion The reduction of natural Tregs observed in blood of HS patients could be the result of Tregs homing to sites of inflammatory hot spots in HS skin. Further studies are justified evaluating the role of circulating Tregs during the evolution of HS lesions and as a biomarker for treatment response.

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The Dual Role of Treg in Cancer

Cited by 79 publications

References 103 publications

Phenotypic Switching of Naïve T cells to Immune-suppressive Treg-like Cells by Mutant KRAS

Phenotypic Switching of Naïve T cells to Immune-suppressive Treg-like Cells by Mutant KRAS

Complement system's role in cancer and its therapeutic potential in ovarian cancer

Frequency of circulating subpopulations of T‐regulatory cells in patients with hidradenitis suppurativa

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