Haplotype Loss of HLA Class I Antigen as an Escape Mechanism from Immune Attack in Lung Cancer

So, Tetsuya; Takenoyama, Mitsuhiro; Mizukami, Makiko; Ichiki, Yoshinobu; Sugaya, Masakazu; Hanagiri, Takeshi; Sugio, Kenji; Yasumoto, Kosei

doi:10.1158/0008-5472.can-04-3787

Cited by 81 publications

(82 citation statements)

References 35 publications

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“…Several reports support the concept of TAA loss as a potential mechanism to escape immunotherapeuticalinduced antitumor response. However, our studies confirm that the escape of resistant variants to CTL may be also independent of TAA loss (29,30). We found in this context that T cell recognition did occur, as revealed by T cell reactivation, including granzyme B, perforin transcription, and exocytosis.…”

Section: Discussionsupporting

confidence: 78%

Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure

Abouzahr

Bismuth

Gaudin

et al. 2006

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

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To investigate tumor resistance to T cell lysis, a resistant variant was selected after specific cytolytic T lymphocytes (CTL) selection pressure. Although the resistant variant triggered perforin and granzyme B transcription in specific CTLs, as well as their degranulation, it exhibited a dramatic resistance to cytotoxic T cell killing. It also displayed strong morphological changes with alterations of the actin cytoskeleton. Electron microscopy analysis revealed a loosen interaction between CTLs and the resistant variant despite the formation of apparently normal conjugates. Transcriptional profiling identified a gene expression signature that distinguished sensitive from resistant tumor targets. More notably, we found that actin-related genes ephrin-A1 and scinderin were overexpressed in resistant target. Silencing of these genes using RNA interference resulted in a restoration of normal cell morphology and a significant attenuation of variant resistance to CTL killing. Our present study shows that a shift in cytoskeletal organization can be used, by tumor cells, as a strategy to promote their resistance after CTL selection pressure.cell-mediated cytotoxicity ͉ ephrin-A1 ͉ scinderin

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Section: Discussionsupporting

confidence: 78%

Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure

Abouzahr

Bismuth

Gaudin

et al. 2006

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

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“…An analysis of immune responses to autologous tumor cells in clinical cancer patients has allowed the identification of various tumor-associated antigens (3,(21)(22)(23)(24)(25)(26). However, there have been several reports about the tumor antigens identified by using CTL from lung cancer patients (27)(28)(29)(30)(31). Three of such reports were about tumor-specific mutated antigens, which was unique to the individual patient.…”

Section: Discussionmentioning

confidence: 99%

Identification of a New Cancer/Germline Gene,KK-LC-1, Encoding an Antigen Recognized by Autologous CTL Induced on Human Lung Adenocarcinoma

et al. 2006

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The purpose of our present study is to identify a tumorspecific antigen capable of inducing a specific cellular immune response in lung cancer patients. We established a lung adenocarcinoma cell line, designated as F1121L, and induced tumor-specific CTL clone H1 from regional lymph node lymphocytes of patient F1121. CTL clone H1 lysed autologous tumor cells in an HLA-B*1507-restricted manner, but not autologous EBV-B, phytohemagglutinin-blast cells, and K562. The CTL clone also recognized allogeneic HLA-B*1501-or 1507-positive lung cancer cell lines in the HLArestricted manner. Using the CTL clone, we identified an antigen-coding gene by cDNA expression cloning technique. The gene consisted of 556 bp, including an open reading frame consisted of 113 amino acids, designated as Kita-kyushu lung cancer antigen 1 (KK-LC-1). A 9-mer peptide (KK-LC-1 76-84 ; RQKRILVNL) was identified as an epitope peptide. The genomic DNA of this antigen was located in chromosome Xq22. A reverse transcription-PCR analysis revealed that the mRNA of this gene was only expressed in the testis among normal tissues. It was expressed in 9 of 18 (50%) allogeneic non-small-cell lung cancer cell lines and in 40 of 100 (40%) non-small-cell lung cancer tissues. We thus identified a new tumor antigen-coding gene categorized as a cancer/germline gene by an autologous lung cancer and CTL system. The new cancer/germline gene was located in Xq22, which is apparently different from the locations of previously reported cancer/germline genes. (Cancer Res 2006; 66(9): 4922-8)

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“…Numerous innate and adaptive immune effector cells participate in the recognition and destruction of cancer cells, a process that is known as cancer immunosurveillance (5)(6)(7). Cancer cells can escape innate and adaptive immune either by immunosubversion or by immunoselection (8)(9)(10)(11)(12). Immunosubversion is a process of active suppression of the immune response by tumor cells.…”

Section: Introductionmentioning

confidence: 99%

“…Immunosubversion is a process of active suppression of the immune response by tumor cells. Tumors use numerous different mechanisms ( further referenced as immunoescape mechanisms) of immunosubversion (8,(13)(14)(15)(16), including down-regulation of MHC class I expression (9,10) and up-regulation of expression of CD95L (16), indoleamine-2,3-dioxygenase (14,15), and arginase-1 or transforming growth factor-h and interleukin (IL)-10 (17). Moreover, a significant expansion of regulatory T (T reg ) cells, which are capable of inhibiting both CD4 + and CD8 + T-cell responses, was observed during progression of many types of tumors both in mice and humans (18).…”

Section: Introductionmentioning

confidence: 99%

Overcoming Immunoescape Mechanisms of BCL1 Leukemia and Induction of CD8+ T-Cell–Mediated BCL1-Specific Resistance in Mice Cured by Targeted Polymer-Bound Doxorubicin

et al. 2008

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BALB/c mice bearing syngeneic BCL1 leukemia, a mouse model of human chronic lymphocytic leukemia, were treated with polymer-bound doxorubicin conjugate targeted with BCL1-specific monoclonal antibody. Such treatment can cure up to 100% of mice and the cured mice show long-lasting resistance to BCL1 leukemia. We show that both CD4 + and CD8 + T cells are required for establishment of the resistance, but only CD8 + T cells are necessary for its maintenance. BCL1 cells express MHC class I and II and also costimulatory molecules CD80 and CD86, which can aid eliciting of antitumor response. On the other hand, BCL1 cells also use several immunoescape mechanisms, such as expression of PD-L1, PD-L2, and interleukin-10. BCL1 cells thus can be recognized by BCL1-specific T cells, but instead of effective priming, such T cells are anergized or deleted by apoptosis. Moreover, BCL1 leukemia progression is accompanied by robust expansion of CD4 + CD25 + Foxp3 + regulatory T (T reg ) cells. Although it has been shown that depletion of T reg cells in tumor-bearing mice can retard tumor growth, direct evidence that expansion of T reg cells can promote tumor growth was lacking. In this study, we provide first direct evidence that expanded T reg cells can indeed promote tumor progression by using mice with selectively expanded T reg cells before inoculation of BCL1 leukemia. Finally, we have also shown that elimination of some immunoescape mechanism (e.g., deletion of T reg ) can significantly improve the therapeutic outcome of chemotherapy. [Cancer Res 2008;68(23):9875-83]

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Haplotype Loss of HLA Class I Antigen as an Escape Mechanism from Immune Attack in Lung Cancer

Cited by 81 publications

References 35 publications

Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure

Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure

Identification of a New Cancer/Germline Gene,KK-LC-1, Encoding an Antigen Recognized by Autologous CTL Induced on Human Lung Adenocarcinoma

Overcoming Immunoescape Mechanisms of BCL1 Leukemia and Induction of CD8+ T-Cell–Mediated BCL1-Specific Resistance in Mice Cured by Targeted Polymer-Bound Doxorubicin

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