Immunomodulatory role of TIITS in respect to cytotoxic lymphocytes in four grades of human glioma

Kumar, Pankaj; Acharya, S. K.; Chatterjee, Sirshendu; Kumari, Annpurna; Chaudhuri, Suhnrita; Singh, Manoj Kumar; Ghosh, Subhasis

doi:10.1016/j.cellimm.2012.05.006

Cited by 8 publications

(7 citation statements)

References 20 publications

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“…T11TS, the sheep erythrocyte derived membrane glycopeptides; a potent immunomodulatory molecule demonstrated remarkable anti‐neoplastic action against ENU induced glioma‐bearing rat model and also in vitro human glioma sample (Chaudhuri et al, , ; Ghosh et al, ; Ghosh, Bhattacharya, Sarkar, Acharya, & Chaudhuri, ; Kumar et al, , ; Mukherjee et al, , , Mukherjee, Ghosh, Sarkar, Mazumdar, Sarkar, et al, ; Mukherjee, Ghosh, Ghosh, & Chaudhuri, ; Sarkar et al, ; Sarkar, Ghosh, Mukherjee, Chaudhuri, & Chaudhuri, ). In our recent work, we have demonstrated for the first time that during gliomogenic shock there was a significant diminution in early phases of hematopoietic cell signaling.…”

Section: Introductionmentioning

confidence: 99%

“…However, the impacts of glioma on hematopoietic machinery have not been explored so far. T11TS, the sheep erythrocyte derived membrane glycopeptides; a potent immunomodulatory molecule demonstrated remarkable anti-neoplastic action against ENU induced glioma-bearing rat model and also in vitro human glioma sample (Chaudhuri et al, 2014(Chaudhuri et al, , 2015Ghosh et al, 2007;Ghosh, Bhattacharya, Sarkar, Acharya, & Chaudhuri, 2010;Kumar et al, 2012Kumar et al, , 2013Mukherjee et al, 2002Mukherjee, Ghosh, Ghosh, & Chaudhuri, 2006;Sarkar et al, 2002;Sarkar, Ghosh, Mukherjee, Chaudhuri, & Chaudhuri, 2004b).…”

Section: Introductionmentioning

confidence: 99%

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T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells

Mondal¹,

Hazra²,

Datta³

et al. 2017

Journal Cellular Physiology

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Combating gliomagenic global immunosuppression is one of the emerging key for improving prognosis in malignant glioma. Apoptosis plays a pivotal role within the adult hematopoietic system particularly in regulating the cells of immune system. Gliomagenic regulation of apoptotic mediators within bone marrow milieu has not been elucidated. We previously demonstrated that administration of membrane glycopeptides T11 target structure (T11TS) not only rejuvenate bone marrow hematopoietic stem cells (BMHSCs) from glioma mediated hibernation by inhibiting gliomagenic overexpression of Ang-1/Tie-2 but also stimulate glioma mediated diminution of expression CD34, c-kit, and Sca-1 markers. In the present study, we investigated the impact of glioma on apoptotic signaling cascades of BMHSCs and consequences following T11TS therapy. Bone marrow smear and Annexin V staining confirm gliomagenic acceleration of apoptotic fate of BMHSCs whereas T11TS treatment in gliomabearing rats disrupted apoptosis of BMHSCs. Flowcytometry, immunoblotting, and immunofluorescence imagining results revealed multi potent T11TS not only significantly downregulates gliomagenic overexpression of Fas, Fas L, Bid, and caspase-8, the pro-apoptotic extrinsic mediators but also strongly inhibits cytosolic release of cytochrome-c, Apf-1, and Bax to deactivate gliomagenic caspase-9, 3 the key intrinsic apoptotic mediators followed by up modulation of anti-apoptotic Bcl-2 in glioma associated HSCs. T11TS is also able to diminish the perforin-granzyme B mediated apoptotic verdict of BMHSCs during gliomagenesis. The antiapoptotic action of T11TS on glioma associated BMHSCs provide a crucial insight into how T11TS exerts its immunomodulatory action against glioma mediated immune devastation. K E Y W O R D Sapoptosis, glioma, HSCs, immunotherapy, T11TS

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells

Mondal¹,

Hazra²,

Datta³

et al. 2017

Journal Cellular Physiology

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“…Efforts towards T-cell signal reconstitution have till date focused on single-target approaches such as CTLA-4 blockade, CD45 repair, etc., however, the effectiveness of T11TS lies in its sequential restoration of dysregulated components of the immunological synapse, triggering activation of both T-cells and macrophages. We have previously shown that in T11TS-treated in vitro glioma samples, cytotoxic lymphocytes apoptosize glioma cells; this was mediated by greater perforin-granzyme secretion and Fas-FasL upregulation as compared to samples not treated with T11TS [48]. Furthermore, a marked rise of CD4?…”

Section: Resultsmentioning

confidence: 94%

“…Our previous work has highlighted reversal of gliomainduced immunosuppressive Th2 cytokine phenotype to the immunepotentiating Th1 phenotype followed by immunehomeostasis upon T11TS administration, i.e., high IL-10, TGF-b levels prevalent in glioma were suppressed [47,48] and low levels of IL-12, IFN-c and TNF-a in glioma were increased after T11TS administration [47]. IL-10 upregulation suppresses CD3 [49], MHC-II [50,51] and CD28 [52], and TGF-b upregulation leads to downregulated MHC-II and CD80 and to CTLA-4 upregulation [50,53].…”

Section: Discussionmentioning

confidence: 99%

The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation

Chaudhuri

Singh²,

Bhattacharya³

et al. 2014

J Neurooncol

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T-cell-mediated immune responses are typically low in conditions of malignant glioma which has been known to cause marked immunesuppression and dysregulate major T-cell signaling molecules. Thus, T-cell-based immunotherapies are currently in vogue in the treatment of malignant glioma. The novel glycopeptide, T11TS/S-LFA-3/S-CD58 has previously been shown by our group to be highly efficacious in glioma abrogation in in vivo and in vitro conditions. This glycopeptide ligands to the costimulatory CD2 molecule on T-cells, causing profound immune stimulation leading to glioma abrogation, suggesting probable involvement of T11TS in modulation of the T-cell signaling pathway. The present study offers a multi-targeted approach towards repair of some of the key components of the immunological synapse at the T-cell-APC interface and is therefore the first of its kind to offer a holistic model of restoration of immunological synapse components so as to trigger T-cells towards activation against glioma. The study thus indicates that the totally dysregulated molecular events at the immunological synapse in glioma are restored back to normal levels with the administration of T11TS, which finally culminates in glioma abrogation. The present study thus delineates an important T-cell signaling approach whereby T11TS acts as an anti-neoplastic agent, thus helping to chart out newer avenues in the fight against gliomas.

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“…Our group for the first time successfully established the role of T11TS as catalyzing cell cycle arrest [5] and also specific apoptotic inducer [6] of the brain tumour cells in animals. T11TS has been documented as orchestrator of cytotoxic T lymphocyte mediated killing of target tumor cell in in vitro studies of human glioma model [10]. In addition, favourable immunomodulation in cytotoxic proteins and other phenotypic markers in grade I, II glioma model have been well documented.…”

Section: Introductionmentioning

confidence: 98%

T11TS Induced Modulation of Macrophages Associated Cytokines TNF-α,VEGF and Apoptototic Protein Bax, Bcl2 Abrogates Tumor Cells in In vitro Grade I,II Human Glioma

Chaudhuri¹,

Chaudhuri²,

Kumari³

2011

J Clin Cell Immunol

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T11 target structure (T11TS), a membrane glycoprotein has been documented with anti-neoplastic activity in glioma bearing animal model in our lab. In this study, we have evaluated the phagocytic potential, expression of VEGF, TNF-α in T11TS treated and untreated macrophages in all four grades of glioma. The data indicates the significant enhancement of phagocytosis in T11TS treated macrophages of Grade I and II glioma. There was significant upregulation in TNF-α and significant down-regulationin VEGF expression in T11TS treated macrophages in grade I and II glioma.We alsoattempted to know any possible apoptotic role of T11TS in tumor cell by comparing Bax and Bcl2 in treated and untreated tumour cell of all four grades. We found significant up-regulation in Bax expression and down-regulation in Bcl2 expression of grade I and II glioma. The outcome may help in pushing this molecule into pharmaceutical domain.

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Immunomodulatory role of TIITS in respect to cytotoxic lymphocytes in four grades of human glioma

Cited by 8 publications

References 20 publications

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells

The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation

T11TS Induced Modulation of Macrophages Associated Cytokines TNF-α,VEGF and Apoptototic Protein Bax, Bcl2 Abrogates Tumor Cells in In vitro Grade I,II Human Glioma

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