Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions

Arreygue-Garcia, Naela; Daneri-Navarro, ́Adrián; Toro-Arreola, Alicia del; Cid-Arregui, Ángel; González-Ramella, Óscar; Jave-Suárez, Luis F; Aguilar‐Lemarroy, Adriana; Troyo-Sanromán, Rogelio; Bravo-Cuéllar, Alejandro; Delgado‐Rizo, Vidal; Garcia-Iglesias, Trinidad; Hernández‐Flores, Georgina; Toro-Arreola, Susana del

doi:10.1186/1471-2407-8-16

Cited by 74 publications

(67 citation statements)

References 61 publications

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“…Indeed, soluble forms of NKG2DLs are present in the serum of cancer patients, and their levels correlate with tumor stage and metastasis (12,20,21,(38)(39)(40)(41), as well as with reduced expression of NKG2D on NK cells and other cytotoxic lymphocytes (11,21,42).…”

Section: Discussionmentioning

confidence: 99%

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Zingoni

Cecere

Vulpis

et al. 2015

The Journal of Immunology

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Genotoxic stress can promote antitumor NK cell responses by upregulating the surface expression of activating ligands on cancer cells. Moreover, a number of studies suggested a role for soluble NK group 2D ligands in the impairment of NK cell tumor recognition and killing. We investigated whether genotoxic stress could promote the release of NK group 2D ligands (MHC class I-related chain [MIC]A and MICB), as well as the molecular mechanisms underlying this event in human multiple myeloma (MM) cells. Our results show that genotoxic agents used in the therapy of MM (i.e., doxorubicin and melphalan) selectively affect the shedding of MIC molecules that are sensitive to proteolytic cleavage, whereas the release of the short MICA*008 allele, which is frequent in the white population, is not perturbed. In addition, we found that a disintegrin and metalloproteinase 10 expression is upregulated upon chemotherapeutic treatment both in patient-derived CD138(+)/CD38(+) plasma cells and in several MM cell lines, and we demonstrate a crucial role for this sheddase in the proteolytic cleavage of MIC by means of silencing and pharmacological inhibition. Interestingly, the drug-induced upregulation of a disintegrin and metalloproteinase 10 on MM cells is associated with a senescent phenotype and requires generation of reactive oxygen species. Moreover, the combined use of chemotherapeutic drugs and metalloproteinase inhibitors enhances NK cell-mediated recognition of MM cells, preserving MIC molecules on the cell surface and suggesting that targeting of metalloproteinases in conjunction with chemotherapy could be exploited for NK cell-based immunotherapeutic approaches, thus contributing to avoid the escape of malignant cells from stress-elicited immune responses

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Section: Discussionmentioning

confidence: 99%

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Zingoni

Cecere

Vulpis

et al. 2015

The Journal of Immunology

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“…Indeed, elevated serum levels of soluble MICA, (19,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) MICB (20,25,29,32) and ULBP2 (21,27) have been detected in cancer patients. In addition, several clinical studies have suggested a correlation between the level of soluble MICA (sMICA) and a poor prognosis.…”

Section: Ul16-binding Protein 2 (Ulbp2) Is One Of the Ligands For Nkgmentioning

confidence: 99%

Diagnostic and prognostic impact of serum‐soluble UL16‐binding protein 2 in lung cancer patients

et al. 2012

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UL16-binding protein 2 (ULBP2) is one of the ligands for NKG2D (NKG2DL). ULBP2 expression is induced in transformed cells and is recognized by immune effector cells via the activating NKG2D immunoreceptor. Soluble forms of NKG2DL have been reported in the serum of patients with several types of cancer. The present study investigated the diagnostic and prognostic significance of serum-soluble ULBP2 (sULBP2) in lung cancer patients. We used flow cytometry to evaluate the surface expression of NKG2DL by various lung cancer cells, while sULBP2 was measured using our original ELISA. In addition, the immunological effect of sULBP2 on peripheral blood mononuclear cells (PBMC) was examined by the 51 Cr release assay. We found that ULBP2 was highly expressed and that the sULBP2 level was elevated in supernatants of cultured non-small-cell lung cancer (NSCLC) cells as well as in the serum of NSCLC patients. ULBP2 levels were especially high in squamous cell carcinoma (SQ) patients. Clinical stage IIIB and IV NSCLC patients with a sULBP2 level ! 8.7 pg/mL showed significantly shorter survival than patients with sULBP2 <8.7 pg/mL. In multivariate analysis, a sULBP2 level ! 8.7 pg/mL (hazard ratio [HR], 2.13; P = 0.038) and clinical stage IV (HR, 2.65; P = 0.019) were independent determinants of a poor outcome. As a possible mechanism, we demonstrated that sULBP2 directly suppresses the cytolytic activity of PBMC. In conclusion, ULBP2 is the most significant NKG2DL for lung cancer, and sULBP2 is useful in the diagnosis of SQ and as a prognostic indicator for patients with advanced NSCLC. (Cancer Sci 2012; 103: 1405-1413

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“…In addition, HPV is able to decrease the secretion of the chemokine IL-8 as well as to diminish the synthesis of IFN-␥ (12). Furthermore, it has been reported that HPV infection is associated with a reduction in the expression of different innate immune receptors, including Tolllike receptor 9 (TLR9) (9), NKp30, NKp46, and NKG2D, diminishing the cytotoxic activity NK cells (2,7). Finally, HPV is also able to inhibit the expression of the zeta chain of T cell receptor complex (CD247) and to induce the release of IL-10, interfering with the activation of Th1 lymphocytes (27,28).…”

mentioning

confidence: 99%

Human Papillomavirus Immunization Is Associated with Increased Expression of Different Innate Immune Regulatory Receptors

Colmenares

Noyola

Monsiváis‐Urenda

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTHuman papillomavirus (HPV) is able to inhibit the secretion of gamma interferon (IFN-γ) and the expression of some immune innate cell receptors. Immunoglobulin-like transcript 2 (ILT2) is a regulatory receptor that seems to participate in the pathogenesis of viral infections. We have studied the expression and function of ILT2 and the expression of other NK cell receptors in 23 healthy women before and after immunization with the quadrivalent HPV (type 6/11/16/18) vaccine (Gardasil). Receptor expression was analyzed by flow cytometry in freshly isolated peripheral blood mononuclear cells as well as afterin vitrostimulation with the quadrivalent HPV (type 6/11/16/18) vaccine. In addition, the regulatory function of ILT2 on cell proliferation and IFN-γ production was analyzed. We found a significant increase in the expression of ILT2 by NK and CD3+CD56+lymphocytes and monocytes after quadrivalent HPV (type 6/11/16/18) vaccine immunization. In addition, thein vitrostimulation with the quadrivalent HPV (type 6/11/16/18) vaccine also increased the proportion of CD3−CD56+ILT2+NK cells. Although the inhibitory function of ILT2 on cell proliferation was enhanced after HPV immunization, thein vitroengagement of this receptor did not affect the synthesis of IFN-γ induced by HPV. Finally, a significant increase in the expression of NKG2D, NKp30, and NKp46 by NK and CD3+CD56+lymphocytes was detected after quadrivalent HPV (type 6/11/16/18) vaccine immunization. Our data indicate that HPV immunization is associated with significant changes in the expression and function of different innate immune receptors, including ILT2, which may participate in the protective effect of HPV vaccines.

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Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions

Cited by 74 publications

References 61 publications

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Diagnostic and prognostic impact of serum‐soluble UL16‐binding protein 2 in lung cancer patients

Human Papillomavirus Immunization Is Associated with Increased Expression of Different Innate Immune Regulatory Receptors

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