Antitumor Activation of Peritoneal Macrophages by Thymosin Alpha-1

Shrivastava, Priyanka; Singh, Sukh Mahendra; Singh, Nisha

doi:10.1081/cnv-200058813

Cited by 3 publications

(4 citation statements)

References 16 publications

(21 reference statements)

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“…An impressive amount of data reported by Shrivastava and his colleagues reveal the benefits of Ta1 to TAM-targeted cancer therapy. [114][115][116][117] They showed that Ta1 prompted the production of IL-1, TNF, reactive oxygen intermediates and NO in TAMs 114,116 and induced M1 TAMs and in turn prolonged the survival time of mice with Dalton lymphoma. 116,117 Finally, we would note the effects of re-polarized TAMs on adaptive immunity.…”

Section: Enhancing M1 Tumoricidal Activity Of Tamsmentioning

confidence: 99%

Anti‐tumour strategies aiming to target tumour‐associated macrophages

et al. 2013

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SummaryTumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAMtargeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAMtargeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy.

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Section: Enhancing M1 Tumoricidal Activity Of Tamsmentioning

confidence: 99%

Anti‐tumour strategies aiming to target tumour‐associated macrophages

et al. 2013

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“…32 As shown by other research groups, the relation between T␣1 and cancer is complex and based also on the direct effect of T␣1 on various immune effector cell types, among which are macrophages and DCs. 9,[33][34][35] As an example, Shrivastava et al have shown that T␣1 activates monocytes, bone marrow-derived macrophages (BMDMs) and tumor-associated macrophages to a tumoricidal state. 33 This effect occurs via the enhancement of their production of macrophageactivating cytokines and other molecules (i.e., IL-1, tumor necrosis factor (TNF), reactive oxygen intermediates (ROI), and nitric oxide (NO)), which act in autocrine manner, with consequent increased pinocytosis, phagocytosis, antigen presentation, and tumor cytotoxicity by these important effector cells.…”

Section: Action On Immune Effector Cellsmentioning

confidence: 99%

“…33 This effect occurs via the enhancement of their production of macrophageactivating cytokines and other molecules (i.e., IL-1, tumor necrosis factor (TNF), reactive oxygen intermediates (ROI), and nitric oxide (NO)), which act in autocrine manner, with consequent increased pinocytosis, phagocytosis, antigen presentation, and tumor cytotoxicity by these important effector cells. 33,34 Peng et al have shown that T␣1 induces the production of IL-6, IL-10, and IL-12 in murine BMDMs through IB kinase (IKK) and mitogen-activated protein kinases (MAPK) pathways. 35 Romani et al have shown that T␣1 upregulates the expression of Toll-like receptor (TLR) 2, 5, 8, and 9 and protects mice from challenge by invasive aspergillosis in a myeloid differentiate factor 88 (MyD88)-dependent way.…”

Section: Action On Immune Effector Cellsmentioning

confidence: 99%

Thymosin α1 and cancer: action on immune effector and tumor target cells

Garaci¹,

Pica²,

Serafino³

et al. 2012

Annals of the New York Academy of Sciences

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Since it was first identified, thymosin alpha 1 (Tα1) has been characterized to have pleiotropic effects on several pathological conditions, in particular as a modulator of immune response and inflammation. Several properties exerted by Tα1 may be attributable to a direct action on lymphoid cells. Tα1 has been shown to exert an immune modulatory activity on both T cell and natural killer cell maturation and to have an effect on functions of mature lymphocytes, including stimulating cytokine production and cytotoxic T lymphocyte-mediated cytotoxic responses. In previous studies we have shown that Tα1 increases the expression of major histocompatibility complex class I surface molecules in murine and human tumor cell lines and in primary cultures of human macrophages. In the present paper, we describe preliminary data indicating that Tα1 is also capable of increasing the expression of tumor antigens in both experimental and human tumor cell lines. This effect, which is exerted at the level of the target tumor cells, represents an additional factor increasing the antitumor activity of Tα1.

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“…15 The recent finding that granulopoiesis and lymphopoiesis in bone marrow are specifically and reciprocally coupled by inflammation 38 makes the control of inflammation a central issue in transplantation. Although T␣1 activates innate cells, including DCs, to an antimicrobial 16 and antitumor state, 39 the attenuation of the immunogenic/inflammatory activity of myeloid DCs by T␣1 through IDO induction qualifies T␣1 as a unique immunoregulatory molecule capable of fine-tuning and controlling the quality of the immune response, which may result in the control of inflammatory response and restoration of protective antimicrobial immunity in the relative absence of GVHD, as seen in mice that received transplants. As chronic inflammation may be linked to cancer development, T␣1 would be expected to work in conditions in which prolonged inflammation may promote cancer.…”

Section: Thymosin ␣1 Activates Ido In Dendritic Cells 2271mentioning

confidence: 99%

Thymosin α1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance

Romani

Bistoni

Perruccio

et al. 2006

Blood

168

151

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IntroductionThe induction of tolerance is central to the maintenance of immune homeostasis. Not only are dendritic cells (DCs) key elements in the development of immunity, but they also participate in the generation and maintenance of immune tolerance. Many studies have demonstrated a pivotal role for the enzyme indoleamine 2,3-dioxygenase (IDO) in immune regulation during infection, pregnancy, autoimmunity, transplantation, and neoplasia. 1,2 IDO is widely expressed in a variety of human tissues as well as in macrophages and DCs and is induced in inflammatory states via type I or type II IFN signaling. Through localized tryptophan deficiency combined with the release of proapoptotic kynurenines, DCs exert an IDO-dependent homeostatic control over the proliferation and survival of peripheral T cells and promote antigen-specific tolerance. 3,4 Murine plasmacytoid DCs (pDCs), which produce and respond to type I IFNs, have been credited with a unique ability to express functional IDO, implying an important role for these cells in the maintenance of peripheral tolerance. 5 DCs are now being exploited to improve vaccine efficacy. 6 Pathogen-pulsed DCs act, indeed, as a potent fungal vaccine in experimental hematopoietic stem cell transplantation (HSCT). 7 Protection is associated with myeloid and T-cell recovery, the activation of CD4 ϩ T-helper type 1 (Th1) lymphocytes, and the concomitant production of IL-10. This cytokine is required for the induction of regulatory T (Treg) cells, which have important functions in immune homeostasis including the onset of transplantation tolerance, inhibition of inflammation, and prevention of graft-versus-host disease (GVHD) lethality and leukemia relapse. [8][9][10] As tolerance is also one major requirement of a successful immune response to fungi, 11-13 tolerogenic DCs, including pDCs, may be pivotal in the generation of some form of dominant regulation that ultimately controls inflammation, pathogen immunity, and tolerance in transplant recipients. 14 Thymosin ␣1 (T␣1) is a naturally occurring thymic peptide 15 that promotes activation and cytokine production in human and murine mature DCs by signaling through Toll-like receptors (TLRs), including TLR9. 16 By influencing the balance of IL-12-and IL-10-producing DCs, T␣1 acts as an immune regulator capable of inducing protective immunity to Aspergillus fumigatus. 16 TLR9 stimulation can also lead to IDO activation via mechanisms including autocrine type I IFN signaling 17,18 and can promote pDC-mediated generation of CD4 ϩ CD25 ϩ cells, 19 which are an essential component of the IDO-dependent protective immunity to fungi. [11][12][13] We hypothesized that T␣1 could affect the balance of immunity and tolerance by DCs and the generation of Treg cells. We assessed here the effects of T␣1 on deriving DCs from bone marrow (murine) or peripheral blood (human) L.R. and P.P. devised the study, critically evaluated the data at regular intervals, and drafted the paper. L.R. takes responsibility for integrity of the work as a whole. K.P....

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Antitumor Activation of Peritoneal Macrophages by Thymosin Alpha-1

Cited by 3 publications

References 16 publications

Anti‐tumour strategies aiming to target tumour‐associated macrophages

Anti‐tumour strategies aiming to target tumour‐associated macrophages

Thymosin α1 and cancer: action on immune effector and tumor target cells

Thymosin α1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance

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