Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma

Hiroishi, Kazumasa; Eguchi, Junichi; Baba, Toshiyuki; Shimazaki, Tomoe; Ishii, Shigeaki; Hiraide, Ayako; Sakaki, Masashi; Doi, Hiroyoshi; Uozumi, Shojiro; Omori, Risa; Matsumura, Takuya; Yanagawa, Tatsuro; Ito, Takayoshi; Imawari, Michio

doi:10.1007/s00535-009-0155-2

Cited by 134 publications

(81 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the magnitude of the TAA-specific CD8 + T cell response (40) and the precursor frequency of TAA-specific T cells (41) correlates with prolonged tumor-free survival in some studies, even very large numbers of TAA-specific T cells do not alter tumor progression in others (42). Therefore, variant peptide vaccines also need to expand an effective portion of the TAAspecific T-cell repertoire, which is dependent on the structure of the variant peptide and the cross-reactivity of the responding T cells (23,24).…”

Section: Discussionmentioning

confidence: 99%

Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens

Jordan

McMahan

Kemmler

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Peptide vaccines enhance the response of T cells toward tumor antigens and represent a strategy to augment antigen-independent immunotherapies of cancer. However, peptide vaccines that include native tumor antigens rarely prevent tumor growth. We have assembled a set of peptide variants for a mouse-colon tumor model to determine how to improve T-cell responses. These peptides have similar affinity for MHC molecules, but differ in the affinity of the peptide-MHC/T-cell receptor interaction with a tumor-specific T-cell clone. We systematically demonstrated that effective antitumor responses are generated after vaccination with variant peptides that stimulate the largest proportion of endogenous T cells specific for the native tumor antigen. Importantly, we found some variant peptides that strongly stimulated a specific T-cell clone in vitro, but elicited fewer tumor-specific T cells in vivo, and were not protective. The T cells expanded by the effective vaccines responded to the wild-type antigen by making cytokines and killing target cells, whereas most of the T cells expanded by the ineffective vaccines only responded to the peptide variants. We conclude that peptide-variant vaccines are most effective when the peptides react with a large responsive part of the tumor-specific T-cell repertoire.

show abstract

Section: Discussionmentioning

confidence: 99%

Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens

Jordan

McMahan

Kemmler

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Further study suggesting a role for CTL responses in HCC are shown by Hiroishi at al., where they determined that a vigorous CD8+ T-cell response against tumor antigens is associated with a prolonged recurrence-free period after treatment with trans-arterial chemoembolization or radiofrequency ablation [45]. They tested CTL response by interferon-3 ELISPOT to a pool of peptide antigens derived from GPC3, NY-ESO-1 and MAGE-1.…”

Section: Immunotherapeutic Gpc3 Vaccinementioning

confidence: 99%

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Allegretta¹,

Filmus²

2011

ACAMC

View full text Add to dashboard Cite

Glypican-3 (GPC3) is a developmentally-regulated oncofetal protein that has been established as a clinically-relevant biomarker for early hepatocellular carcinoma (HCC). It is one of the first transcripts to appear during malignant hepatocyte transformation, and is expressed at the protein level in approximately half of high-grade dysplastic macronodules in cirrhotic liver. Several studies show it is expressed in most (75 to 100%) of HCCs confirmed by histopathology. The protein is anchored to the hepatocyte membrane by a glycosyl-phosphatidylinositol (GPI) anchor and shows consistent membrane immunostaining pattern, making it a viable target for immunotherapeutic approaches. Targeting GPC3 for therapeutic intervention is a promising approach for the clinical management of HCC and selected other tumors that express the marker.

show abstract

“…Parallel analysis of T cell responses specific for a panel of different tumor-associated antigens (glypican-3, NY-ESO-1, and MAGE-1) has demonstrated that the magnitude of tumor antigen-specific T cell responses represent the only significant prognostic factor for a prolonged tumor-free interval after interventional therapy for patients with HCC. This indicates that strong tumor-specific CD8+ T cell responses can control the recurrence of HCC [28] . …”

Section: Presence Of Antigen-specific T Cell Responsesmentioning

confidence: 99%

Immune Responses in Hepatocellular Carcinoma

Korangy

Höchst

Manns

et al. 2010

Dig Dis

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related deaths worldwide and efficient treatment options are urgently needed. Based on its pathogenesis as well as a number of correlative studies, immunotherapy represents a potential therapeutic option for patients with HCC. However, tumors have also evolved numerous immune escape mechanisms, such as the generation of cells with immune suppressor functions, including regulatory T cells and myeloid-derived suppressor cells. It has been shown that these suppressor cells mask tumor-specific immune responses in patients with HCC. We propose that targeting suppressor cells either alone or in combination with conventional immunotherapy should be further evaluated in HCC patients.

show abstract

Strong CD8+ T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma

Cited by 134 publications

References 31 publications

Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens

Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

Immune Responses in Hepatocellular Carcinoma

Contact Info

Product

Resources

About