Immune system: a double-edged sword in cancer

Narendra, Bodduluru Lakshmi; Reddy, Kasala Eshvendar; Saladi, Shantikumar; Sistla, Ramakrishna

doi:10.1007/s00011-013-0645-9

Cited by 153 publications

(102 citation statements)

References 78 publications

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“…Conventional wisdom places them on the other side of a balancing act with Tregs and additional regulatory cells in solid cancers [108]. We thus explored the possibility of a perturbation of the relative frequencies of CD8 + and FOXP3 + T cells in BCL, but found no evidence of a deficit of the former when compared to the control groups.…”

Section: Discussionmentioning

confidence: 96%

Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma

et al. 2014

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The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

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Section: Discussionmentioning

confidence: 96%

Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma

et al. 2014

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“…CXCL10 has been most robustly studied in the context of activation and/or recruitment of immune cells including T lymphocytes, NK cells, dendritic cells, macrophages and B cells through its cognate receptor CXCR3. As ligation of CXCR3 on these immune cells leads to the induction of cytokines such as IFN γ , interleukin-2 (IL-2) or tumor necrosis factor- α (TNF- α ), which would promote cellular immune responses in the tumors, one would imagine this chemokine to have antitumor effects [38]. But once again, the expression of this immune mediator appears to be a double-edged sword within the microenvironment of PC.…”

Section: Discussionmentioning

confidence: 99%

Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer

Delitto

Perez

Han

et al. 2015

Cancer Immunol Immunother

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The cancer microenvironment allows tumor cells to evade immune surveillance through a variety of mechanisms. While interferon-γ (IFNγ) is central to effective antitumor immunity, its effects on the microenvironment are not as clear and have in some cancers been shown to induce immune checkpoint ligands. The heterogeneity of these responses to IFNγ remains poorly characterized in desmoplastic malignancies with minimal inflammatory cell infiltration, such as pancreatic cancer (PC). Thus, the IFNγ response within and on key cells of the PC micro-environment was evaluated. IFNγ induced expression of human leukocyte antigen (HLA) class I and II on PC cell lines, primary pancreatic cancer epithelial cells (PPCE) and patient-derived tumor-associated stroma, concomitant with an upregulation of PDL1 in the absence of CD80 and CD86 expression. As expected, IFNγ also induced high levels of CXCL10 from all cell types. In addition, significantly higher levels of CXCL10 were observed in PC specimens compared to those from chronic pancreatitis, whereby intratumoral CXCL10 concentration was an independent predictor of poor survival. Immunohistochemical analysis revealed a subset of CXCR3-positive cancer cells in over 90 % of PC specimens, as well as on a subset of cultured PC cell lines and PPCE, whereby exposure to CXCL10 induced resistance to the chemotherapeutic gemcitabine. These findings suggest that IFNγ has multiple effects on many cell types within the PC microenvironment that may lead to immune evasion, chemoresistance and shortened survival.

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“…CD8 + cytotoxic T lymphocytes (CTLs) facilitate immunosurveillance by T cell receptor (TCR) recognition of antigens bound to major histocompatibility complex (MHC)-I on antigen presenting cells and when activated, produce interferon gamma (IFN-γ), perforin and granzyme B that contribute to tumor cell cytolysis [46]. In addition to CD8 + CTLs, various CD4 + T cells, including regulatory T (Treg) and T helper 17 (Th17) CD4 + T cell subsets have emerged as key players across a variety of diseases involving inflammation, including cancer.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis

et al. 2016

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Lung cancer is a leading cause of cancer-related deaths worldwide. Lung cancer risk factors, including smoking and exposure to environmental carcinogens, have been linked to chronic inflammation. An integral feature of inflammation is the activation, expansion and infiltration of diverse immune cell types, including CD4+ T cells. Within this T cell subset are immunosuppressive regulatory T (Treg) cells and pro-inflammatory T helper 17 (Th17) cells that act in a fine balance to regulate appropriate adaptive immune responses.In the context of lung cancer, evidence suggests that Tregs promote metastasis and metastatic tumor foci development. Additionally, Th17 cells have been shown to be an integral component of the inflammatory milieu in the tumor microenvironment, and potentially involved in promoting distinct lung tumor phenotypes. Studies have shown that the composition of Tregs and Th17 cells are altered in the tumor microenvironment, and that these two CD4+ T cell subsets play active roles in promoting lung cancer progression and metastasis.We review current knowledge on the influence of Treg and Th17 cells on lung cancer tumorigenesis, progression, metastasis and prognosis. Furthermore, we discuss the potential biological and clinical implications of the balance among Treg/Th17 cells in the context of the lung tumor microenvironment and highlight the potential prognostic function and relationship to metastasis in lung cancer.

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Immune system: a double-edged sword in cancer

Cited by 153 publications

References 78 publications

Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma

Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma

Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer

Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis

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