Magnitude and polarization of P53-specific T-helper immunity in connection to leukocyte infiltration of colorectal tumors.
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 (IFNgamma, TNFalpha, 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 INFgamma or other cytokines such as IL-10. Patients who exhibited p53-specific IFNgamma-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.
D000328:Adult; D000368:Aged; D002465:Cell Movement; D016764:Cell Polarity; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000032:analysis; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D007074:Immunoglobulin G; D016159:Tumor Suppressor Protein p53; D017493:Leukocyte Common Antigens