Increased number of intratumoral IL-17+ cells, a harbinger of the adverse prognosis of triple-negative breast cancer

Qian, Xiaolong; Xu, Peng; Zhang, Yi-Qian; Song, Yuan-Ming; Li, Yaqing; Li, Weidong; Jiang, Cheng‐Ying; Shen, Biyu; Zhang, Xinmin; Zhang, Lina; Fu, Li; Guo, Xiaojing

doi:10.1007/s10549-020-05540-6

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…Whether this is reason enough to let oneś fears run wild, culminating eventually into heptadecaphobia, remains questionable. Strong pro-tumorigenic effects [109][110][111]114,[119][120][121] Possible antitumorigenic effects [112] Strong pro-tumorigenic effects [106,107,113,118 Largely unknown effects Possible antitumorigenic effects [168] Possible pro-tumorigenic effects [171] Largely unknown effects Possible pro-tumorigenic effects [171] IL-22 Potential pro-tumorigenic effects [173,175,176,178,180,181] Possible pro-tumorigenic effects [151,172] HCC IL-17A Strong pro-tumorigenic effects [189][190][191][192][197][198][199][200][201] Strong pro-tumorigenic effects [187,188,193,195] IL-17F…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, treatment of mice with recombinant IL-17A increases the tumor burden of previously implanted breast cancer cell lines [106], and IL-17A antibody treatment reduces the tumor size [107]. Likewise, IL-17A levels are increased in patients suffering from breast cancer compared with healthy controls [108], and infiltration of IL-17A-positive cells presents itself as a poor prognostic factor in humans [109][110][111].…”

Section: Overall Impact Of Il-17amentioning

confidence: 99%

“…Two-colored boxes indicate divergent functions. In general, current literature suggests a strong protumorigenic role of IL-17A[106,107,[109][110][111]113,114,[118][119][120][121]124] and IL-22[128][129][130][131][132][133][134], although in one study, contrasting observations were made[127]. (A) Macrophages[114,115], T C 17 cells[113], T H 17 cells[112], and cd T cells[116,117] were found to be major producers of IL-17A in breast cancer.…”

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confidence: 97%

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Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis

et al. 2021

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Cancer is one of the leading causes of death worldwide. When cancer patients are diagnosed with metastasis, meaning that the primary tumor has spread to at least one different site, their life expectancy decreases dramatically. In the past decade, the immune system´s role in fighting cancer and metastasis has been studied extensively. Importantly, immune cells and inflammatory reactions generate potent antitumor responses but also contribute to tumor development. However, the molecular and cellular mechanisms underlying this dichotomic interaction between the immune system and cancer are still poorly understood. Recently, a spotlight has been cast on the distinct subsets of immune cells and their derived cytokines since evidence has implicated their crucial impact on cancer development. T helper 17 cell (T H 17) cells, which express the master transcriptional factor Retinoic acid-receptor-related orphan receptor gamma t, are among these critical cell subsets and are defined by their production of type 3 cytokines, such as IL-17A, IL-17F, and IL-22. Depending on the tumor microenvironment, these cytokines can also be produced by other immune cell sources, such as T cytotoxic 17 cell, innate lymphoid cells, NKT cells, or cd T cells. To date, a lot of data have been collected describing the divergent functions of IL-17A, IL-17F, and IL-22 in malignancies. In this comprehensive review, we discuss the role of these T H 17-and non-T H 17derived type 3 cytokines in different tumor entities. Furthermore, we will provide a structured insight into the strict regulation and subsequent downstream mechanisms of these cytokines in cancer and metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Overall Impact Of Il-17amentioning

confidence: 99%

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confidence: 97%

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Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis

et al. 2021

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“…Upon overexpression, IL-17 can activate tumor microangiogenesis through its signal transduction pathways, resulting in increased tumor secretion of VEGFA, thereby promoting tumor progression. 46 TLRs trigger multiple signaling pathways involving nuclear factor B, IRFs, and MAPKs to produce various cytokines with important roles in diseases such as cancer. 47 Inhibition of TLR signaling can suppress human BC cell viability, invasion, and migration.…”

Section: Discussionmentioning

confidence: 99%

<p>Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer</p>

Wu¹,

Luo²,

Li³

2020

BCTT

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“…In addition to IL-17 production for host defense against tumors, MAIT cells are able to directly eliminate tumor cells through the expression of perforin and granzyme B after activation through their TCRs, which are specific against target tumor cells expressing MR1 in complex with metabolite antigens in the plasma membrane [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 28 , 30 , 31 , 41 , 47 ]. Moreover, IL-17A is known to stimulate tumor cell proliferation and metastasis in non-small-cell lung cancer and breast cancer [ 48 , 49 , 50 , 51 , 52 ]. Perhaps, this is one of the mechanisms associated with the poor prognosis of HCC and CRC patients with tumors of IL-17A-expressing MAIT cells.…”

Section: Mait Cells and Il-17 Family Membersmentioning

confidence: 99%

MR1-Restricted T Cells in Cancer Immunotherapy

Flores-Villanueva

Sobhani

Wang

et al. 2020

Cancers

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Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells’ TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.

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Increased number of intratumoral IL-17+ cells, a harbinger of the adverse prognosis of triple-negative breast cancer

Cited by 14 publications

References 32 publications

Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis

Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis

<p>Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer</p>

MR1-Restricted T Cells in Cancer Immunotherapy

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Increased number of intratumoral IL-17+ cells, a harbinger of the adverse prognosis of triple-negative breast cancer

Cited by 14 publications

References 32 publications

Rationalizing heptadecaphobia: TH17 cells and associated cytokines in cancer and metastasis

Rationalizing heptadecaphobia: TH17 cells and associated cytokines in cancer and metastasis

<p>Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer</p>

MR1-Restricted T Cells in Cancer Immunotherapy

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Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis

Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis