Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2588
© 2004 American Society of Clinical Oncology

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Abstract

Investigation of a possible escape mechanism in colorectal cancer patients

Univ. of Wuerzburg, Depts of Surgery, Molecular Oncoimmunology, and Pathology, Wuerzburg; Germany

2588

Background: Anti-tumor specific immune responses are modulated during tumor development via different escape mechanisms abrogating immunological tumor destruction. We analyzed p53 specific immune responses in colorectal cancer patients depending on UICC stage and characterized their regulatory T cell functions independent of the p53 mutational status. Methods: Peripheral blood lymphocytes (PBMCs) from patients (UICC-stage I-IV, n=24) were stimulated with 10 pools of synthetic overlapping p53 peptides encompassing the full length wild-type (wt) p53 sequence and Il-10 and IFN- expression was assessed (ELISA, ELISPOT). PBMCs, tumor specific cells, and tumor specimens were further characterized (cytospins, FACS, immunohistology).Results: Lymphocyte stimulation with the peptide pools resulted in distinct residues inducing a Th2 (IL-10, n=24) or Th1 (IFN-, n=10) type response. T cells from UICC III (n=7) and IV (n=7) patients expressed more IL-10 in response to p53 peptide (residues 291–330) than those in UICC I and II (n=6) (26 and 62 spots/10⁵ cells vs 14 spots/10⁵ cells, respectively), indicating that the UICC stage may be crucial in IL-10 production in response to p53 peptides. In contrast, residues 331–370 led to IFN- production but no correlation was observed between UICC stage and Th1 response. Markedly elevated amounts of CD4+, CD25+, and CD56+ cells in the PBMCs, as well as intensified staining for p53 (clone DO-7) were observed in patients expressing higher levels of IL-10 (cytospins, immunohistology). Conclusions: Within the whole p53 protein sequence comparably more determinants inducing a Th2 type immune response were observed suggesting that the type of the tumor specific immune response to p53 depends on presentation and recognition of specific wt p53 residues. IL-10 production seems to overweigh IFN- indicating that specific p53 epitopes may directly influence the outcome of immunological surveillance in colorectal cancer patients. This study offers new insights in a possible mechanism facilitating the tumor to escape immune surveillance by inducing rather a Th2 (tolerance) than Th1 type response (destruction) through p53 overexpression.

No significant financial relationships to disclose.

Abstract presentation from the 2004 ASCO Annual Meeting