Involvement of NK Cells against Tumors and Parasites

Papazahariadou, M.; Athanasiadis, Georgios; Papadopoulos, E.; Symeonidou, Isaia; Hatzistilianou, M.; Castellani, M.L.; Bhattacharya, K.; Shanmugham, L.N.; Conti, Pio; Frydas, S.

doi:10.1177/172460080702200208

Cited by 14 publications

(5 citation statements)

References 92 publications

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“…Finally, an increased number of macrophages would also enhance ADCC of tumor cells in vivo , as T. cruzi ‐specific antibodies could mediate tumor cell killing in vitro . Furthermore, tumor cytotoxicity mediated by NK cells should not be excluded, as they are strongly activated during T. cruzi infection, and often displays potent antitumor activity.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

Ubillos

Freire

Berriel

et al. 2015

Intl Journal of Cancer

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Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasitederived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU). We found that vaccination with T. cruzi epimastigote lysates strongly inhibits tumor development in both animal models. Rats immunized with T. cruzi antigens induce activation of both CD4 1 and CD8 1T cells and splenocytes from these animals showed higher cytotoxic responses against tumors as compared to rats receiving adjuvant alone. Tumor-associated immune responses included increasing number of CD11b/c 1 His48 2 MHC II 1 cells corresponding to macrophages and/or dendritic cells, which exhibited augmented NADPH-oxidase activity. We also found that T. cruzi lysate vaccination developed antibodies specific for colon and mammary rat cancer cells, which were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in vitro. Anti-T. cruzi antibodies cross-reacted with human colon and breast cancer cell lines and recognized 41/60 (68%) colon cancer and 38/63 (60%) breast cancer samples in a series of 123 human tumors. Our results suggest that T. cruzi antigens can evoke an integrated antitumor response involving both the cellular and humoral components of the immune response and provide novel insights into the understanding of the intricate relationship between parasite infection and tumor growth.

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Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

Ubillos

Freire

Berriel

et al. 2015

Intl Journal of Cancer

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“…The pathogenesis of chronic Chagas disease is still only partly understood although there is a general consensus that the host immune response plays a key role in determining the distinct clinical forms of the disease. There are several immunological events that seem to influence the outcome of chronic Chagas disease, including cytotoxic mechanisms mediated by CD8 + T cells that are relevant for the development of cardiac disease, regulatory cells such as CD4 + CD25 High Treg and NKT cells, as well as cytotoxic NK cells that play a protective role [4–9].…”

Section: Introductionmentioning

confidence: 99%

Strategy to Assess the Overall Cytokine Profile of Circulating Leukocytes and its Association with Distinct Clinical Forms of Human Chagas Disease

et al. 2008

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Herein we have employed an alternative strategy to assess the cytokine patterns of circulating leukocytes and correlate dominant cytokine profiles with indeterminate‐IND and cardiac‐CARD clinical forms of Chagas disease. We have first calculated median percentages of cytokine‐positive leukocytes of our study sample to establish, for each cytokine‐positive cell population, the cut‐off edge that would segregate ‘low’ and ‘high’ cytokine producers to build colour diagrams and draw a panoramic cytokine chart. Using this approach we demonstrated that most IND individuals presented a dominant regulatory cytokine profile, whereas CARD individuals displayed a dominant inflammatory cytokine pattern. In addition, radar chart analysis confirmed the dichotomic cytokine balance between IND and CARD groups and further allowed the identification of the relative contribution of each cell population for the global cytokine pattern. Data analysis demonstrated that CD4+ T cells were the major cell population defining the regulatory profile in IND, whereas monocytes and CD4+ T cells determined the inflammatory cytokine pattern in CARD individuals. Interestingly, in vitro stimulation with trypomastigote Trypanosoma cruzi antigen was able to invert the cytokine balances in IND and CARD groups. Upon antigenic stimulation, changes in the frequencies of IL‐10‐producing CD4+ T cells and monocytes drove IND individuals towards an inflammatory pattern and CARD towards a regulatory cytokine profile. A similar inversion could be found after in vivo treatment of IND and CARD individuals with benzonidazole. Altogether, these findings shed some light into the complex cytokine network underlying the immunopathogenesis of Chagas disease and provide putative immunological biomarkers of disease severity and therapeutic response.

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“…In the privileged cancer context, NK cells were largely represented [21,35] as well as soluble HLA-G molecules [31,32] suggesting a potential role of HLA-G molecules in NK cells signaling and probably in the modulation of their function. Membranous HLA-G1 molecules have been described as activators of NF-кB pathway toward NK cell lines [9].…”

Section: Discussionmentioning

confidence: 99%

Soluble HLA-G induces NF–кB activation in natural killer cells

et al. 2010

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Human leukocyte antigen (HLA)-G is an immunomodulatory molecule discovered for the first time in the maternal-fetal interface. In cancer context, where high number of natural killer (NK) cells is described, the presence of HLA-G in its soluble form is thought to be essential for NK cells signaling. To evaluate intracellular signaling in NK cells upon HLA-G soluble forms stimulation, we investigate the role of soluble HLA-G (HLA-G5- and HLA-G1 shedding form) stimulation on classical nuclear factor (NF)-kappaB pathway activation. We reported that these two forms of soluble HLA-G could activate NF-kappaB in NK cells. NF-kappaB activation in NK cells does implicate neither phosphatidylinositol 3-kinase (PI3K) nor MEK (MAP kinase kinase) as demonstrated after specific inhibition experiments. We demonstrated elsewhere that NF-kappaB activation in NK cells is not implicated in cytotoxicity inhibition by HLA-G. Our findings may suggest the important role played by NF-kappaB activation after soluble HLA-G stimulation in other NK cells function.

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Involvement of NK Cells against Tumors and Parasites

Cited by 14 publications

References 92 publications

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

Strategy to Assess the Overall Cytokine Profile of Circulating Leukocytes and its Association with Distinct Clinical Forms of Human Chagas Disease

Soluble HLA-G induces NF–кB activation in natural killer cells

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