Selective changes in expression of HLA class I polymorphic determinants in human solid tumors.

Natali, P. G.; Nicotra, Maria Rita; Bigotti, A.; Venturo, Irene; Marcenaro, L; Giacomini, Patrizio; Russo, Carlo

doi:10.1073/pnas.86.17.6719

Cited by 111 publications

(54 citation statements)

References 26 publications

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“…2b) showed an almost complete downregulation of HLA-C [measured using mAb L31 (Grassi et al, 1991;Setini et al, 1996), which is specific for HLA-C open conformers]. The bulk of MHC class I, measured by mAb W6/32 (Natali et al, 1989), specific for all trimericconformation class I molecules, showed a reduction compatible with the silencing of HLA-C and the conservation of HLA-A and -B, as already seen by RNA analysis. Among the HIV-1 receptors, CD4 and CXCR4 expression was unaltered by the treatment, whilst CCR5 shows a minor reduction in expression (not evidenced by RNA analysis).…”

Section: Hla-c Sirna Silencing In Cell Linesmentioning

confidence: 81%

“…VSV-G env and the HIV-1 env and rev sequences of the HIV-1 subtype B strains QH0692.42, AC10, 6535.5 and pRHPA4259.7 and subtype D strain NDK were obtained through the MRC CFAR NIBSC programme. mAbs L31 (Grassi et al, 1991;Setini et al, 1996) and W6/32 (Natali et al, 1989) were provided by Dr P. Giacomini (Laboratory of Immunology, Regina Elena Cancer Institute CRS, Rome, Italy). mAb M01 16/4/1 (anti-p24) was donated from Polymun, Germany.…”

Section: Discussionmentioning

confidence: 99%

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HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

Baroni

Matucci

Scarlatti

et al. 2009

Journal of General Virology

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The hypothesis that open conformers of HLA-C on target cells might directly exert an effect on their infectability by human immunodeficiency virus (HIV) has been suggested previously. This was tested by exploiting the peculiar specificity of monoclonal antibody (mAb) L31 for HLA-C open conformers to show that normal levels of Env-driven fusion were restored in HLA-C transfectants of a major histocompatibility complex-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is now confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs) from 11 healthy donors. Infectability by HIV (strains IIIB and Bal and primary isolates) was significantly reduced (P50.016) in silenced cells compared with cells that maintained HLA-C expression in 10 of the 11 PBL donors. Normal infectability was resumed, together with HLA-C expression, when the effect of siRNA interference waned after several days in culture. Additional confirmation of the HLA-C effect was obtained in several assays employing HLA-C-positive and -negative cell lines, a number of HIV strains and also pseudoviruses. In particular, viruses pseudotyped with env genes from HIV strains AC10 and QH0692.42 were assayed on siRNA-silenced lymphocytes from three healthy donors: the differences in infection with pseudoviruses were even higher than those observed in infections with normal viruses. INTRODUCTIONThree recent whole-genome association studies have demonstrated and confirmed that minor allele variants of singlenucleotide polymorphisms in the major histocompatibility complex (MHC; in particular HLA-C) gene regions are associated with a lower viral load at the set point and additionally with delayed human immunodeficiency virus type 1 (HIV-1) disease progression (Fellay et al., 2007;Limou et al., 2009;van Manen et al., 2009). These findings, which echo a previous report on the association between HLA-C alleles and rapid progression to AIDS (Carrington et al., 1999), have prompted wide speculations on the role of HLA (and HLA-C in particular) in HIV biology and immunology. HLA-C differs from HLA-A and -B because HIV-1 selectively downregulates HLA-A and -B, but does not significantly affect HLA-C (or HLA-E). Therefore, infected cells display reduced detection by both cytotoxic lymphocytes and natural killer (NK) cells (Cohen et al., 1999). The hypothesis that HLA-C might exert an effect directly on HIV infectivity was originally suggested by De Santis et al. (1996), exploiting the peculiar specificity of monoclonal antibody (mAb) L31 to show that normal levels of Env-driven fusion were restored in HLA-C transfectants (Grassi et al., 1991;Setini et al., 1996) of an MHC-deleted (fusion-incompetent) cell line. The physiological relevance of this finding is confirmed in this report, where small interfering RNA (siRNA) technology was used to silence HLA-C expression in peripheral blood lymphocytes (PBLs), the natural target of HIV-1. Two different kinds o...

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Section: Hla-c Sirna Silencing In Cell Linesmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

Baroni

Matucci

Scarlatti

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

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“…Some of the well-recognized tumor immune evasion mechanisms include failure of tumor antigen recognition (4-6), modulation of MHC molecule expression (7,8), improper activation of antigen-presenting cells (APC; refs. 1, 9), failure of lymphocyte homing (1,10), and production of immunosuppressive cytokines (11,12).…”

Section: Introductionmentioning

confidence: 99%

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Gujar

Marcato

Pan

et al. 2010

Molecular Cancer Therapeutics

105

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Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response-mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity capable of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells facilitates the recognition of tumor antigens by promoting the display of otherwise inaccessible tumorspecific immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reovirus, DCs produce IL-1α, IL-1β, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, M-CSF, MIG, MIP-1α, RANTES, TNF-α, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturation; and migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs also acquire the capacity to prime tumor antigen-specific transgenic T cells in vitro and intrinsic antitumor T-cell response in vivo. Further, reovirus virotherapy augments the efficacy of DC-or T cell-based anticancer immunotherapies and synergistically enhances the survival in tumor-bearing mice. Most importantly, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host against subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reovirus oncotherapy-initiated antitumor immune responses represent an anticancer therapeutic entity that can maintain a long-term cancer-free health even after discontinuation of therapy.

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“…12 Immunohistochemical (IHC) studies in different types of solid tumors have demonstrated defects in HLA class Ia expression. 13 Moreover, selective down-regulation of the HLA class I A or B locus also has been observed in GC, colon carcinoma, and laryngeal carcinoma. 14,15 However, most IHC studies of functional HLA expression on tumor samples have been performed with either monomorphic-determinant and/or allele-specific antibodies directed against HLA class Ia, because locusspecific antibodies are not available commercially.…”

mentioning

confidence: 99%

Down‐regulation of locus‐specific human lymphocyte antigen class I expression in Epstein–Barr virus‐associated gastric cancer

Dutta

Gupta

Mazumder

et al. 2006

Cancer

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Clinical course and prognosis are variable among patients with chronic inflammatory demyelinating polyneuropathy (CIDP), whereas the extent of axonal degeneration is the major prognostic factor. We studied the effects of sera from CIDP patients on axonal growth in cultured mouse dorsal root ganglion neurons. Compared with control sera, CIDP sera prominently suppressed axonal outgrowth of dorsal root ganglion neurons and shortened axonal length. The inhibitory activity was abolished by adding Y27632, a Rho‐kinase inhibitor. These findings suggest that CIDP sera inhibit axonal elongation by Rho‐kinase activation, and some serum factors may be responsible for development of axonal degeneration in CIDP. Ann Neurol 2009;66:694–697

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Selective changes in expression of HLA class I polymorphic determinants in human solid tumors.

Cited by 111 publications

References 26 publications

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

HLA-C is necessary for optimal human immunodeficiency virus type 1 infection of human peripheral blood CD4 lymphocytes

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Down‐regulation of locus‐specific human lymphocyte antigen class I expression in Epstein–Barr virus‐associated gastric cancer

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