Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy

Host anti-tumor immunity can be hindered by various mechanisms present within the tumor microenvironment, including the actions of myeloid-derived suppressor cells (MDSCs). We investigated the role of the CCR2/MCP-1 pathway in MDSC-associated tumor progression in murine lung cancer models. Phenotypic profiling revealed maximal expression of CCR2 by tumor-resident MDSCs, and MCP-1 by transplanted TC1 tumor cells, respectively. Use of CCR2-knockout (CCR2-KO) mice showed dependence of tumor growth on CCR2 signaling. Tumors in CCR2-KO mice had fewer CCR2low MDSCs, CD4 T cells and Tregs than WT mice, and increased infiltration by CD8 T cells producing IFN-γ and granzyme-B. Effects were MDSC specific, since WT and CCR2-KO conventional T (Tcon) cells had comparable proliferation and production of inflammatory cytokines, and suppressive functions of WT and CCR2-KO Foxp3+ Treg cells were also similar. We used a thioglycolate-induced peritonitis model to demonstrate a role for CCR2/MCP-1 in trafficking of CCR2+ cells to an inflammatory site, and showed the ability of a CCR2 antagonist to inhibit such trafficking. Use of this CCR2 antagonist promoted anti-tumor immunity and limited tumor growth. In summary, tumor cells are the prime source of MCP-1 that promotes MDSC recruitment, and our genetic and pharmacologic data demonstrate that CCR2 targeting may be an important component of cancer immunotherapy.

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Tissue-Resident Lymphocytes: Implications in Immunotherapy for Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22010232 ◽

2020 ◽

Vol 22 (1) ◽

pp. 232

Author(s):

Ji Won Han ◽

Seung Kew Yoon

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Population ◽

Tumor Immunity ◽

Checkpoint Inhibitors ◽

Γδ T Cells ◽

Treg Cells ◽

Inkt Cells ◽

Mait Cells ◽

Invariant Natural Killer

Hepatocellular carcinoma (HCC) is a hard-to-treat cancer. The recent introduction of immune checkpoint inhibitors (ICIs) provided viable options to treat HCC, but the response rate is currently not sufficient. Thus, a better understanding of ICI-responding cells within tumors is needed to improve outcomes of ICI treatment in HCC. Recently, tissue-resident memory T (TRM) cells were defined as a subset of the memory T cell population; this cell population is actively under investigation to elucidate its role in anti-tumor immunity. In addition, the role of other tissue-resident populations such as tissue resident regulatory T (Treg) cells, mucosal associated invariant T (MAIT) cells, γδ T cells, and invariant natural killer T (iNKT) cells in anti-tumor immunity is also actively being investigated. However, there is no study that summarizes recent studies and discusses future perspectives in terms of tissue resident lymphocytes in HCC. In this review, we summarize key features of tissue-resident lymphocytes and their role in the anti-tumor immunity. Additionally, we review recent studies regarding the characteristics of tissue-resident lymphocytes in HCC and their role in ICI treatment and other immunotherapeutic strategies.

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Progress in research into the role of abnormal glycosylation modification in tumor immunity

Immunology Letters ◽

10.1016/j.imlet.2020.11.003 ◽

2021 ◽

Vol 229 ◽

pp. 8-17

Author(s):

Hui-min Liu ◽

Le-le Ma ◽

Bo Cao ◽

Jun-zhi Lin ◽

Li Han ◽

...

Keyword(s):

Tumor Immunity ◽

Abnormal Glycosylation

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The Role of Th17 Response in COVID-19

Cells ◽

10.3390/cells10061550 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1550

Author(s):

Diana Martonik ◽

Anna Parfieniuk-Kowerda ◽

Magdalena Rogalska ◽

Robert Flisiak

Keyword(s):

Immune Response ◽

Treg Cells ◽

The Body ◽

System Response ◽

Th17 Response ◽

Monocyte Chemoattractant Protein 1 ◽

Acute Infectious Disease ◽

Cytokine Cascade ◽

Necrosis Factor

COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells. This review focuses on a Th17 pathway in the course of the immune response in COVID-19, and explores plausible targets for therapeutic intervention.

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