CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination

Cheng, Wen-Fang; Hung, Chien Fu; Lin, Ken Y.; Ling, Morris; Juang, Jyuhn‐Huarng; He, Li; Lin, Cheng-Tao; Wu, T. C.

doi:10.1038/sj.gt.3301982

Cited by 55 publications

(53 citation statements)

References 49 publications

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“…30 This subline, generated after three cycles of immunoselection in vaccinated mice, has lower MHC class I expression, making it resistant to vaccines effective in the original more immunogenic TC-1 cells. Vaccines able to target the subline rely mainly on CD8 T cells and NK cells.…”

Section: Resultsmentioning

confidence: 99%

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Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

et al. 2015

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Section: Resultsmentioning

confidence: 99%

“…TC-1 P3 (A15) cells, 30 obtained from Dr. T.-C. Wu (Baltimore, MD, USA) and the NK-sensitive cell line YAC-1 (ATCC, Manassas, VA) were grown in RPMI 1640 medium containing 10% fetal calf serum and antibiotics.…”

Section: Cell Linesmentioning

confidence: 99%

Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

et al. 2015

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“…27 Further, it has recently been reported by our laboratory that the up-regulation of the MHC class I expression can also occur in vivo during a long-term immunotherapy of the TC-1/A9 (MHC class I negative) tumours, probably due to the production of IFNg by the immune cells in the tumour microenviroment and its vicinity. 32 To investigate the possibility that CpG ODN 1826 in our experimental setting with the TC-1/A9 tumours acts after up-regulation of the MHC class I molecule expression due to the concomitant immunity also through the CD8 1 -dependent mechanism, we performed the in vivo depletion studies.…”

Section: Discussionmentioning

confidence: 99%

“…26 The TC-1/P3C10 cell line with reduced expression of MHC class I was cloned from a subline of TC-1/P3 with a reduced level of the MHC class I expression. 27 The TC-1 cell sublines with downmodulated MHC class I expression were obtained from TC-1 tumours developed in immunized mice. They mimic tumour cell variants that escaped from the selection pressure mediated by the specific immune response due to concomitant tumour immune reaction.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I‐deficient and ‐proficient HPV16‐associated tumours

Reiniš

Šímová

Bubenı́k

2005

Intl Journal of Cancer

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Unmethylated oligodeoxynucleotides containing guanine-cytidine dimers (CpG ODN) have been described as potent inducers of selected antitumour immune responses and the immunotherapeutic efficacy of CpG ODN has been examined either alone or as a vaccine adjuvant. We hypothesized that CpG ODN therapy could be an effective tool for immunotherapy of not only conventional MHC class I 1 tumours but also of those tumours that have lost MHC class I expression during their progression. To address this hypothesis, we employed the animal model resembling MHC class I-proficient and -deficient human papilloma virus (HPV) 16-associated tumours. A cell line transformed with HPV16 E6 and E7 oncogenes, TC-1, as a prototype of MHC class I-positive line, and its MHC class I-deficient sublines TC-1/A9 and TC-1/P3C10 were injected into syngeneic C57BL/6 mice and the growing tumours were subjected to immunotherapy with CpG ODN 1826. The therapy started either 1 day after the challenge with the tumour cells or later, when the tumours had reached a palpable size. In both settings, CpG ODN 1826 significantly reduced the growth of MHC class I-proficient and -deficient tumours. Furthermore, we demonstrated that CpG ODN 1585, whose mechanism of action preferably involves indirect activation of the natural killer cells, induced regression of the MHC class I-deficient tumours TC1/A9 but not of the MHC class I-proficient tumours TC-1. This study infers that synthetic CpG ODN have a potential for the therapy of both MHC class I-proficient and -deficient tumours and thus could be also used against tumours that tend to down-regulate their MHC class I expression. ' 2005 Wiley-Liss, Inc.Key words: HPV16; immunotherapy; CpG oligodeoxynucleotides; MHC class I restriction One of the most important and frequent events in the course of the tumour development is a partial or total loss of the MHC class I expression on the tumour cells. [1][2][3] This loss represents an obstacle in the development of efficient immunotherapy of tumours as well as possible explanation for failures of some experimental antitumour immunotherapies based on induction of the Tcell-mediated cytotoxic immune response in clinical trials. Therefore, there is a need for immunotherapeutic protocols that would also be effective for MHC class I-negative tumours. 4,5 Unmethylated oligodeoxynucleotides harboring guanine-cytidine dimers (CpG ODN) that mimic the bacterial DNA are good candidates for such therapeutic agents, since they have been described as potent inducers of the innate and adaptive immune responses, providing the missing ''danger signal'' through the Toll-like receptor 9 (TLR 9) involving pathway. 6 In tumour immunology, CpG ODN have been used in a number of animal studies as adjuvants in experimental vaccinations 7-10 for ex vivo preparation of cellular vaccines as they induce maturation of dendritic cells [11][12][13] and for the therapy of the residual disease after chemotherapy or tumour resection. 14 Moreover, repeated direct intratumoral administration of CpG ODN si...

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“…32 Briefly, 1 Â 10 7 BHK21 cells were infected with 5 Â 10 7 IU of SINrep5, SINrep5-E7, SINrep5-CRT, or SINrep5-CRT/ E7 particles. The transfected BHK21 cells were collected 40-44 h after infection.…”

Section: Enzyme-linked Immunosorbent Assaymentioning

confidence: 99%

Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity

Cheng

Lee

et al. 2006

Cancer Gene Ther

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Alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. In this study, we used the replication-defective vaccine vector SIN replicon particles from a new packaging cell line (PCL) to develop SIN replicon particles encoding calreticulin (CRT) linked to a model tumor antigen, human papillomavirus type 16 (HPV16) E7 protein. The linkage of CRT to E7 in SIN replicon particles resulted in a significant increase in E7-specific CD8 þ T-cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated mice. SINrep5-CRT/E7 replicon particles enhanced presentation of E7 through the major histocompatibility complex (MHC) class I pathway by infecting dendritic cells (DCs) directly and pulsing DCs with lysates of cells infected by SINrep5-CRT/E7 replicons. Vaccination of immunocompromised (BALB/c nu/nu) mice with SINrep5-CRT/E7 replicon particles also generated significant reduction of lung tumor nodules, suggesting that antiangiogenesis may contribute to the antitumor effect of SINrep5-CRT/E7 replicon particles. Furthermore, SINrep5-CRT/E7 replicon particles generated long-term in vivo tumor protection effects and antigen-specific memory immunities. We concluded that the CRT strategy used in the context of SIN replicon particles facilitated the generation of a highly effective vaccine for cancer prophylaxis and immunotherapy.

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CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination

Cited by 55 publications

References 49 publications

Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I‐deficient and ‐proficient HPV16‐associated tumours

Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity

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