Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity

Nishikawa, Hiroyoshi; Tanida, Koji; Ikeda, Hiroaki; Sakakura, Miho; Miyahara, Yoshihiro; Aota, Takumi; Mukai, Katsumi; Watanabe, Masato; Kuribayashi, Kagemasa; Old, Lloyd J.; Shiku, Hiroshi

doi:10.1073/pnas.251547298

Cited by 63 publications

(91 citation statements)

References 41 publications

(40 reference statements)

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“…We have recently proposed that a category of serologically defined self-Ags constitutes Ags recognized by both CD4 ϩ CD25 ϩ naturally occurring regulatory T cells and CD4 ϩ Th cells (9 -12). These self-Ags were identified by serological identification of Ags by recombinant expression cloning (SEREX), 5 a widely used serological cloning method to detect tumor Ags (9,13,14). Immunogenic tumor-derived molecules are detected by IgG Abs in the sera of hosts bearing cognate tumors by screening phage libraries prepared from cDNA of tumor cells.…”

Section: N Aturally Occurring Cd4mentioning

confidence: 99%

IFN-γ Controls the Generation/Activation of CD4+CD25+ Regulatory T Cells in Antitumor Immune Response

Nishikawa¹,

Kato

Tawara³

et al. 2005

The Journal of Immunology

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Immunization with serological identification of Ags by recombinant expression cloning (SEREX)-defined self-Ags leads to generation/activation of CD4+CD25+ regulatory T cells with suppressive activities and enhanced expression of Foxp3. This is associated with increased susceptibility to pulmonary metastasis following challenge with syngeneic tumor cells and enhanced development of 3-methylcholanthrene-induced primary tumors. In contrast, coimmunization with the same SEREX-defined self-Ags mixed with a CTL epitope results in augmented CTL activity and heightened resistance to pulmonary metastasis, both of which depend on CD4+ Th cells. These active regulatory T cells and Th cells were derived from two distinct CD4+ T cell subsets, CD4+CD25+ T cells and CD4+CD25− T cells, respectively. In the present study, IFN-γ was found to abrogate the generation/activation of CD4+CD25+ regulatory T cells by immunization with SEREX-defined self-Ag. CD4+CD25+ T cells from these IFN-γ-treated mice failed to exhibit immunosuppressive activity as measured by 1) increased number of pulmonary metastasis, 2) enhanced development of 3-methylcholanthrene-induced primary tumors, 3) suppression of peptide-specific T cell proliferation, and 4) enhanced expression of Foxp3. The important role of IFN-γ produced by CD8+ T cells was shown in experiments demonstrating that CD4+CD25+ T cells cotransferred with CD8+ T cells from IFN-γ−/− mice, but not from wild-type BALB/c mice, became immunosuppressive and enhanced pulmonary metastasis when recipient animals were subsequently immunized with a SEREX-defined self-Ag and a CTL epitope. These findings support the idea that IFN-γ regulates the generation/activation of CD4+CD25+ regulatory T cells.

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Section: N Aturally Occurring Cd4mentioning

confidence: 99%

IFN-γ Controls the Generation/Activation of CD4+CD25+ Regulatory T Cells in Antitumor Immune Response

Nishikawa¹,

Kato

Tawara³

et al. 2005

The Journal of Immunology

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“…However, it should be noted that other categories of SEREX antigens, such as the overexpressed HER-2/neu protein, are being targeted with some success in the treatment of breast carcinomas (Bernhard et al, 2002). SEREX antigens can also be used as adjuvants to boost the immune response to other tumour antigens (Nishikawa et al, 2001).…”

mentioning

confidence: 99%

A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

et al. 2004

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Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT -PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis nongerminal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types.

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“…Furthermore, our data support the idea that CD4 ϩ T cells induced at earlier stages of tumor growth help the generation of antibody responses that occur later. In contrast, antigens present at earlier stages of tumor development may elicit both cellular and humoral responses (31). Although it with DTH response of naive mice.…”

Section: Discussionmentioning

confidence: 99%

“…remains unclear whether a similar robust antibody response would develop against less immunogenic tumor-associated self antigens, such antigens when up-regulated in cancers can generate detectable antibody responses (31). In addition, new mutations occurring during tumor progression may cause strongly immunogenic mutant antigens.…”

Section: Discussionmentioning

confidence: 99%

Genetic changes occurring in established tumors rapidly stimulate new antibody responses

Spiotto

Reth

Schreiber

2003

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

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Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity

Cited by 63 publications

References 41 publications

IFN-γ Controls the Generation/Activation of CD4+CD25+ Regulatory T Cells in Antitumor Immune Response

IFN-γ Controls the Generation/Activation of CD4+CD25+ Regulatory T Cells in Antitumor Immune Response

A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein

Genetic changes occurring in established tumors rapidly stimulate new antibody responses

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