Abstract:
:Necrotic cells are known to activate the innate immune system and trigger inflammation by releasing damage associated molecular patterns (DAMPs). However, how necrotic cells influence the induction of antigen-specific CD8(+) T cell-mediated adaptive immune responses under sterile conditions, in the absence of pathogen associated molecular patterns (PAMPs), remains poorly understood. Here, we examined antigen-specific CD8(+) T-cell responses to primary sterile necrotic tumor cells both in vitro and in vivo. We found that primary necrotic cells alone fail to generate CD8(+) T cell-dependent immune responses toward cell-associated antigens. We show that necrotic cells trigger CD8(+) T-cell immunity only in the presence of PAMPs or analogs, such as p(dI-dC) and/or unmethylated CpG DNA. The electroporation of tumor cells with these PAMPs prior to necrosis induction triggered antigen-specific CD8(+) T-cell responses through a TLR9/MyD88-dependent pathway. In addition, we found that necrotic cells contain factors that can block the cross-priming of CD8(+) T cells even under non-sterile conditions and can serve as a possible mechanism of immunosuppression. These results suggest that antigen-specific CD8(+) T-cell responses to primary necrotic tumor cells can be induced in the presence of PAMPs and thus have a substantial impact on the development of antitumor vaccination strategies.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Gamrekelashvili J,Ormandy LA,Heimesaat MM,Kirschning CJ,Manns MP,Korangy F,Greten TFdoi
10.4161/onci.21098subject
Has Abstractpub_date
2012-10-01 00:00:00pages
1017-1026issue
7eissn
2162-4011issn
2162-402Xpii
2012ONCOIMM0198journal_volume
1pub_type
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