Tumor-induced thymic involution via inhibition of IL-7Rα and its JAK-STAT signaling pathway: Protection by black tea

Mandal, Deba Prasad; Lahiry, Lakshmishri; Bhattacharyya, Arindam; Bhattacharyya, Sankar; Sa, Gaurisankar; Das, Tanya

doi:10.1016/j.intimp.2005.09.005

Cited by 22 publications

(15 citation statements)

References 48 publications

(68 reference statements)

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“…This indicates that thymocyte development was arrested at the DN stage of differentiation. It has been observed that the impaired Jak/Stat signaling pathways and the decrease in Bcl-XL and A1 in the thymus of tumor bearers could contribute to abnormal T-cell differentiation and tumor-induced thymic atrophy [6,22,23]. Also, it has been suggested that Notch-1 and Jagged-1 signaling pathways can induce the apoptosis of thymocytes and influence the thymus development of the tumor bearer [5].…”

Section: Discussionmentioning

confidence: 99%

“…During the development of bladder cancer, cell-mediated immune responses cease to function normally [2,3,4]. Previous studies have shown that this is also true for many other types of tumors, including gliomas and Ehrlich's ascites carcinoma [5,6]. In these cases, T-cell apoptosis can inhibit antitumor activity and reduce the size of the thymus and thymic cellularity.…”

Section: Introductionmentioning

confidence: 99%

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Disruption of the Thymic Microenvironment Is Associated with Thymic Involution of Transitional Cell Cancer

Song¹,

Yu²,

Wang³

et al. 2013

Urol Int

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Introduction: During bladder tumorigenesis, thymopoiesis is usually downregulated. Considering that the thymus is the site of most T-cell development, this phenomenon may be related to thymic involution. However, the mechanisms involved in this phenomenon remain to be elucidated. Materials and Methods: An MB 49 murine bladder tumor model was used to identify mechanisms that might underlie this process. Results: The thymuses of tumor-bearing mice showed less cellularity than those of healthy mice. Involution was found to be associated with less proliferation and more apoptosis of thymic epithelial cells (TEC). Foxn1, KGF, and IL-7, three factors known to be involved in thymic development, were also downregulated in the thymuses of tumor bearers. When these mice were intravenously injected with KGF, the thymic microenvironment, thymopoiesis, and T-cell differentiation all returned to near normal status. Conclusions: The decreases in thymopoiesis and impaired T-cell differentiation may be attributable to changes in the thymic microenvironment. Improving the function of TEC, rather than T-cell progenitors, should be the focus of therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Disruption of the Thymic Microenvironment Is Associated with Thymic Involution of Transitional Cell Cancer

Song¹,

Yu²,

Wang³

et al. 2013

Urol Int

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“…The EACs were sorted by negative selection using anti-CD3 and anti-CD16 antibody coated micro-beads (Milteny Biotech). Before inoculation, more than 98% of the CD16-/CD3-negative cells were morphologically characterized as EAC by Wright staining [19,20]. …”

Section: Methodsmentioning

confidence: 99%

“…Annexin-V + cells were regarded as apoptotic cells [19,20]. To prevent the overlapping of fluorescent emission spectra of 7-AAD - PE and PerCP - PI, the spectral patterns of respective fluorochrome pairs were compensated during acquisition of flowcytometric data.…”

Section: Methodsmentioning

confidence: 99%

“…Both human patients and experimental animals with advanced cancer often exhibit a poorly functioning immune system [12-15], manifested by decreased T cell proliferation [16], alteration in signal-transducing molecules [17,18], reduced CD4 + :CD8 + ratios, and deficient production of Th-1 cytokines [16,19,20]. These alterations correlate with the severity of disease and with poor survival.…”

Section: Introductionmentioning

confidence: 99%

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Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner via an immuno-modulatory circuit

Saha

Hossain

Mukherjee

et al. 2013

BMC Complement Altern Med

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BackgroundComplementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. However, the molecular mechanisms underneath the anti-cancer effect, if any, of these medicines have still remained unexplored. To this end we attempted to evaluate the efficacy of calcarea carbonica, a homeopathic medicine, as an anti-cancer agent and to delineate the detail molecular mechanism(s) underlying calcerea carbonica-induced tumor regression.MethodsTo investigate and delineate the underlying mechanisms of calcarea carbonica-induced tumor regression, Trypan blue dye-exclusion test, flow cytometric, Western blot and reverse transcriptase-PCR techniques were employed. Further, siRNA transfections and inhibitor studies were used to validate the involvement of p53 pathway in calcarea carbonica-induced apoptosis in cancer cells.ResultsInterestingly, although calcarea carbonica administration to Ehrlich’s ascites carcinoma (EAC)- and Sarcoma-180 (S-180)-bearing Swiss albino mice resulted in 30-35% tumor cell apoptosis, it failed to induce any significant cell death in ex vivo conditions. These results prompted us to examine whether calcarea carbonica employs the immuno-modulatory circuit in asserting its anti-tumor effects. Calcarea carbonica prevented tumor-induced loss of effector T cell repertoire, reversed type-2 cytokine bias and attenuated tumor-induced inhibition of T cell proliferation in tumor-bearing host. To confirm the role of immune system in calcarea carbonica-induced cancer cell death, a battery of cancer cells were co-cultured with calcarea carbonica-primed T cells. Our results indicated a "two-step" mechanism of the induction of apoptosis in tumor cells by calcarea carbonica i.e., (1) activation of the immune system of the host; and (2) induction of cancer cell apoptosis via immuno-modulatory circuit in p53-dependent manner by down-regulating Bcl-2:Bax ratio. Bax up-regulation resulted in mitochondrial transmembrane potential loss and cytochrome c release followed by activation of caspase cascade. Knocking out of p53 by RNA-interference inhibited calcarea carbonica-induced apoptosis thereby confirming the contribution of p53.ConclusionThese observations delineate the significance of immuno-modulatory circuit during calcarea carbonica-mediated tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea carbonica into immunotherapeutic strategies for effective tumor regression.

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Interleukin (IL)-7 Signaling in the Tumor Microenvironment

Bednarz−Misa

Bromke

Krzystek−Korpacka

2021

Advances in Experimental Medicine and Biology

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Tumor-induced thymic involution via inhibition of IL-7Rα and its JAK-STAT signaling pathway: Protection by black tea

Cited by 22 publications

References 48 publications

Disruption of the Thymic Microenvironment Is Associated with Thymic Involution of Transitional Cell Cancer

Disruption of the Thymic Microenvironment Is Associated with Thymic Involution of Transitional Cell Cancer

Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner via an immuno-modulatory circuit

Interleukin (IL)-7 Signaling in the Tumor Microenvironment

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