Immunoglobulin Fc fragment tagging allows strong activation of endogenous CD4 T cells to reshape the tumor milieu and enhance the antitumor effect of lentivector immunization

Yuan Hong, Yibing Peng, Haiyan Xiao, Chael Mi, David Munn, Yukai He

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A major problem with current cancer vaccines is that the induction of CD8 immune responses is rarely associated with antitumor benefits, mainly owing to multiple immune suppressions in established tumor lesions. In this study, we investigated if and how activation of endogenous CD4 T cells could be achieved to influence the suppressive tumor milieu and antitumor effect. We engineered a lentivector (lv) to express a nominal fusion Ag composed of hepatitis B surface protein and IgG2a Fc fragment (HBS-Fc-lv) to increase the magnitude of CD8 response but, more importantly, to induce effective coactivation of CD4 T cells. We found that, remarkably, immunization with HBS-Fc-lv caused significant regression of established tumors. Immunologic analysis revealed that, compared with HBS-lv without Fc fragment, immunization with HBS-Fc-lv markedly increased the number of functional CD8 and CD4 T cells and the level of Th1/Tc1-like cytokines in the tumor while substantially decreasing the regulatory T cell ratio. The favorable immunologic changes in tumor lesions and the improvement of antitumor effects from HBS-Fc-lv immunization were dependent on the CD4 activation, which was Fc receptor mediated. Adoptive transfer of CD4 T cells from the HBS-Fc-lv-immunized mice could activate endogenous CD8 T cells in an IFN-γ-dependent manner. We conclude that endogenous CD4 T cells can be activated by lv expressing Fc-tagged Ag to provide another layer of help - that is, creating a Th1/Tc1-like proinflammatory milieu within the tumor lesion to boost the effector phase of immune responses in enhancing the antitumor effect.

Original languageEnglish (US)
Pages (from-to)4819-4827
Number of pages9
JournalJournal of Immunology
Volume188
Issue number10
DOIs
StatePublished - May 15 2012

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Immunoglobulin Fc Fragments
Immunization
T-Lymphocytes
Neoplasms
Cancer Vaccines
Adoptive Transfer
Fc Receptors
Regulatory T-Lymphocytes
Hepatitis B
Membrane Proteins
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Immunoglobulin Fc fragment tagging allows strong activation of endogenous CD4 T cells to reshape the tumor milieu and enhance the antitumor effect of lentivector immunization. / Hong, Yuan; Peng, Yibing; Xiao, Haiyan; Mi, Chael; Munn, David; He, Yukai.

In: Journal of Immunology, Vol. 188, No. 10, 15.05.2012, p. 4819-4827.

Research output: Contribution to journalArticle

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