Memory Th1 cells augment tumor-specific CTL following transcutaneous peptide immunization

Cancer Res. 2008 May 15;68(10):3941-9. doi: 10.1158/0008-5472.CAN-08-0032.


Targeting dendritic cells in vivo by transcutaneous peptide immunization (TCI) represents an efficient immunization strategy to induce tumor-specific CTL because it reflects the physiologic conditions occurring during pathogen infection. Here we show that including a Th1 peptide in TCI can activate preexisting memory Th1 (mTh1) responses and thereby enhance the CTL response. For this purpose, peptide-25, a major Th1 epitope of Ag85B from Mycobacterium tuberculosis, was selected. We adoptively transferred peptide-25-specific mTh1 cells and hgp100-specific naive CTL (pmel-1 TCR transgenic) into C57BL/6 mice. Subsequently, mice were transcutaneously immunized with CTL peptide (hgp100) and Th1 peptide (peptide-25). Five days after TCI, the frequency and function of pmel-1 cells was monitored by intracellular IFN-gamma staining, ELISPOT, and in vivo cytotoxicity assays. TCI efficiently expanded hgp100-specific, IFN-gamma-producing, strongly cytotoxic CD8(+) T cells. Concurrent activation of mTh1 cells by peptide-25 induced a 1.5-fold increase in the number of hgp100-specific CTL with enhanced effector functions. Furthermore, TCI elicited not only prophylactic but also therapeutic antitumor responses that were augmented by peptide-25. These results show that TCI facilitates peptide-specific activation of CD4(+) T cells, responsible for the augmenting effect of peptide-25 on the hgp100-specific CTL response. Because a significant proportion of the Japanese population has been vaccinated with Bacillus Calmette-Guerin, they are likely to possess Ag85B- or peptide-25-specific mTh1 cells. Therefore, concomitant activation of Ag85B- or peptide-25-specific mTh1 cells together with tumor-specific CTL by TCI might augment antitumor immune responses in a sizeable fraction of patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Line, Tumor
  • Epitopes / chemistry
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides / chemistry*
  • Skin Neoplasms / pathology*
  • T-Lymphocytes, Cytotoxic / cytology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology*


  • Epitopes
  • Peptides
  • Interferon-gamma