<p>Although the low-risk human papillomaviruses (HPVs), including HPV11, are mainly associated with low-grade lesions, they are also implicated in otolaryngologic malignancies and lung carcinomas. Nonetheless, T cell responses to the low-risk HPVs remain poorly understood. This study investigated HPV11 E6/7-specific T cell responses in C57BL/6 mice challenged with TC-1 tumor cells expressing HPV11 E6/7 proteins (TC-1.HPV11 E6/7). We identified two major CD8<sup>+</sup> T cell epitopes, HPV11 E6<sub>41-55</sub> (AEIYAYAYKNLKVVW, p11) and E6<sub>85-99</sub> (YAPTVEEETNEDILK, p22). We next demonstrated that IFNα-matured bone marrow-derived dendritic cells (BMDCs) loaded with peptides p11 or p22 induced p11- and p22-specific CD8<sup>+</sup> T cell responses, respectively. Furthermore, the administration of p11- or p22-loaded BMDCs matured with IFNα or BMDCs generated in the presence of p38 inhibitor/IL-15 and matured with TNFα, IL-1β, and prostaglandin E2, suppressed TC-1.HPV11.E6/7 tumor progression with increased infiltrations of p11- and p22-specific IFNγ<sup>+</sup>, TNFα<sup>+</sup>, and granzyme B<sup>+</sup> CD8<sup>+</sup> T cells in the tumors. In addition, BMDCs loaded with both peptide epitopes, p11 and p22, were more effective than BMDCs loaded with single epitopes in the suppression of TC-1.HPV11 E6/7 tumor progression. Data from this study will help with the rational design of therapeutic strategies for the diseases associated with HPV11 infection.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Preclinical efficacy of dendritic cells loaded with newly identified HPV11 E6-derived CD8+ T cell epitopes

  • Laurie Baert,
  • Chao Gu,
  • Agnes Yang,
  • HyeMee Joo,
  • Richard Kennedy,
  • Kieth Knutson,
  • David G. Lott,
  • SangKon Oh

摘要

Although the low-risk human papillomaviruses (HPVs), including HPV11, are mainly associated with low-grade lesions, they are also implicated in otolaryngologic malignancies and lung carcinomas. Nonetheless, T cell responses to the low-risk HPVs remain poorly understood. This study investigated HPV11 E6/7-specific T cell responses in C57BL/6 mice challenged with TC-1 tumor cells expressing HPV11 E6/7 proteins (TC-1.HPV11 E6/7). We identified two major CD8+ T cell epitopes, HPV11 E641-55 (AEIYAYAYKNLKVVW, p11) and E685-99 (YAPTVEEETNEDILK, p22). We next demonstrated that IFNα-matured bone marrow-derived dendritic cells (BMDCs) loaded with peptides p11 or p22 induced p11- and p22-specific CD8+ T cell responses, respectively. Furthermore, the administration of p11- or p22-loaded BMDCs matured with IFNα or BMDCs generated in the presence of p38 inhibitor/IL-15 and matured with TNFα, IL-1β, and prostaglandin E2, suppressed TC-1.HPV11.E6/7 tumor progression with increased infiltrations of p11- and p22-specific IFNγ+, TNFα+, and granzyme B+ CD8+ T cells in the tumors. In addition, BMDCs loaded with both peptide epitopes, p11 and p22, were more effective than BMDCs loaded with single epitopes in the suppression of TC-1.HPV11 E6/7 tumor progression. Data from this study will help with the rational design of therapeutic strategies for the diseases associated with HPV11 infection.