Magnitude and polarization of P53‐specific T‐helper immunity in connection to leukocyte infiltration of colorectal tumors

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Abstract
The tumor antigen p53 is mutated frequently and overexpressed in colorectal cancer. As a result, patients with this type of cancer commonly display p53‐specific T‐helper (Th) immunity. Examination of the cytokines produced by these Th‐cells showed that a majority of the proliferative p53‐specific T cell cultures produced none of the key cytokines (IFNγ, TNFα, IL‐4, IL‐5 or IL‐10), indicating that these p53‐specific Th‐responses are not polarized. In patients who exhibited p53‐specific reactivity against multiple p53‐epitopes, non‐polarized responses could be found side by side with polarized Th‐responses that produced INFγ or other cytokines such as IL‐10. Patients who exhibited p53‐specific IFNγ‐producing Th cell‐immunity before surgical excision of the tumor displayed higher numbers of tumor infiltrating intraepithelial leukocytes (p = 0.04) than patients lacking such responses, suggesting that the systemic presence of p53‐specific Th‐cells positively affects local tumor‐immunity. Our data concerning the polarization‐state of p53‐specific Th immunity in colorectal cancer patients support the use of vaccine formulations that induce strong Th1‐polarized p53‐specific immunity to ensure proper (re‐)programming of the anti‐tumor response.