Tumour MHC class I downregulation and immunotherapy (Review)

Bubenı́k, Jan

doi:10.3892/or.10.6.2005

Cited by 91 publications

(97 citation statements)

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“…It has been reported that CD8 ϩ T cell responses against infected targets is dependent on the level of expression of HLA class I molecules. For example, a known mechanism of evasion of the host's immune system through suppression of CD8 ϩ responses is the down-regulation of expression of HLA class I molecules during viral infections and with tumors (41)(42)(43)(44). Of note, down-regulation of the expression of HLA class I molecules by enterobacterial infection, including Salmonella, Yersinia, and Klebsiella infection, has also been reported (45).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Human HLA-E-Restricted CD8+ T Cell Subset in Volunteers Immunized withSalmonella entericaSerovar Typhi Strain Ty21a Typhoid Vaccine

Salerno-Gonçalves

Fernández-Viña

Lewinsohn³

et al. 2004

The Journal of Immunology

147

180

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Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4−CD56− T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-γ production. Increases in the net frequency of IFN-γ spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-γ production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Identification of a Human HLA-E-Restricted CD8+ T Cell Subset in Volunteers Immunized withSalmonella entericaSerovar Typhi Strain Ty21a Typhoid Vaccine

Salerno-Gonçalves

Fernández-Viña

Lewinsohn³

et al. 2004

The Journal of Immunology

147

180

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“…However, approximately 40-90% of human tumors derived from various MHC class I positive tissues have been reported to be MHC class I deficient. MHC class I downregulation is an important mechanism of tumor escape from T cellmediated immune responses 13 and can result in failure of immunotherapy. MHC-unrestricted gdT cells represent a promising new concept in immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to ab T cell-mediated cytotoxicity. 12,13 gdT cells exhibit potent MHC-unrestricted lytic activity against different tumor cells in vitro, suggesting their potential utility as anticancer therapy. 5,14,15 ZOL significantly inhibited, although not completely, the proliferation of SCLC cells transplanted subcutaneously into nude mice.…”

mentioning

confidence: 99%

Cytotoxic effects of γδ T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy

Satô

Kimura

Segawa

et al. 2005

Intl Journal of Cancer

133

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Nitrogen containing-bisphosphonates (N-BPs), widely used to treat bone diseases, have direct antitumor effects via the inactivation of Ras proteins. In addition to the direct antitumor activities, N-BPs expand gdT cells, which exhibit major histocompatibility complex-unrestricted lytic activity. BPs accumulate intermediate metabolites which may be tumor antigens in target cells. The purpose of our study was to clarify the cytotoxicity of gd T cells expanded ex vivo by the most potent N-BP, zoledronate (ZOL). Especially, we focused on the importance of pretreatment against target cells also with ZOL; 1 mM ZOL plus IL-2 increased the absolute number of gdT cells 298-768 fold for 14 days incubation. The small cell lung cancer and fibrosarcoma cell lines pretreated with 5 mM ZOL showed a marked increase in sensitivity to lysis by gdT cells. While, untreated cell lines were much less sensitive to lysis by gdT cells. Video microscopy clearly demonstrated that gdT cells killed target cells pre-treated with ZOL within 3 hr. Pretreatment with 80 mg/kg ZOL also significantly enhanced the antitumor activity of gdT cells in mice xenografted with SBC-5 cells. These findings show that ZOL significantly stimulated the proliferation of gdT cells and that gdT cells required pre-treatment with ZOL for cytotoxic activity against target cells. ' 2005 Wiley-Liss, Inc.

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“…(iii) Transplantable murine tumors are selected for good MHC class I expression and thus are very sensitive to a HPV-specific CTL response, while in humans several escape mechanisms of the transformed cells are described, e.g., selective down-regulation of MHC expression and interference with cell signalling and cytokine production. 34,35 Therefore, the combination of the vaccine with a local/lesional inflammatory response induction could highly improve the vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)

Kaufmann

Nieland

Jochmus

et al. 2007

Intl Journal of Cancer

116

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Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric viruslike particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1-and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 lg or 250 lg) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. ' 2007 Wiley-Liss, Inc.Key words: cervical cancer; clinical trial; immunization; antibody; T cell Genital infection with human papillomavirus (HPV) is one of the most common sexually transmitted diseases. Various molecular and epidemiological studies have documented a correlation between infection with ''high risk'' HPV types and premalignant or malignant tumors of the anogenital tract. 1,2 It is widely acknowledged that a causal relationship exists between persistent HPV infection and development of cervical intraepithelial neoplasia (CIN) and cervical cancer. 3,4 There are over 100 known papillomavirus types that are stratified into low and high risk, based on their association with malignant and invasive lesions. More than 95% of invasive cervical cancers are positive for HPV-DNA, mainly from HPV types 16 (50%) and 18 (20%). Moreover, HPV16 can be detected in 30270% of all HPV-positive high grade CIN patients. 5,6 The prevalence of HPV16 in other intraepithelial neoplasias is even higher, e.g., 70280% in high grade vulvar intraepithelial neoplasia. 7 Whereas for low grade CIN a high spontaneous recovery rate is observed 6,8 high grade CIN regress less often particular at higher age when lesions are more persistent. 9 Because of the potential progression of high grade CIN to invasive cancer, 10 a thorough evaluation consisting of colp...

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Tumour MHC class I downregulation and immunotherapy (Review)

Cited by 91 publications

References 0 publications

Identification of a Human HLA-E-Restricted CD8+ T Cell Subset in Volunteers Immunized withSalmonella entericaSerovar Typhi Strain Ty21a Typhoid Vaccine

Identification of a Human HLA-E-Restricted CD8+ T Cell Subset in Volunteers Immunized withSalmonella entericaSerovar Typhi Strain Ty21a Typhoid Vaccine

Cytotoxic effects of γδ T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy

Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)

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