ABSTRACT
BACKGROUND/AIM: The aim of this study was to explore whether the treatment effect or immune response to a cancer vaccine can be predicted by the percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs) after vaccination. PATIENTS AND METHODS: Sixteen patients (9 men, 7 women; median age 61.5 years) enrolled in the CHP-MAGE-A4 cancer vaccine clinical trial who had a fixed dose (300 µg of CHP-MAGE-A4 cancer vaccine and 0.5 Klinische Einheit (KE) of OK432 and received at least four vaccinations were investigated. Safety, immune response, and clinical effects were assessed before and after the cancer vaccination. RESULTS: Treg ratios that remained low both before and after vaccination were associated with a good prognosis, and a low Treg/CD4 lymphocyte ratio 7-weeks after the initial vaccination was correlated with a better prognosis. CONCLUSION: The Treg ratio following vaccination appears to have some utility for predicting patient prognosis.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cancer Vaccines/immunology , Neoplasms/immunology , T-Lymphocytes, Regulatory/immunology , Vaccination , Adult , Aged , Cancer Vaccines/administration & dosage , Female , Forkhead Transcription Factors/immunology , Forkhead Transcription Factors/metabolism , Humans , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-2 Receptor alpha Subunit/metabolism , Kaplan-Meier Estimate , Leukocytes, Mononuclear/immunology , Lymphocyte Count , Male , Middle Aged , Neoplasms/therapy , Outcome Assessment, Health Care/methods , Prognosis , T-Lymphocytes, Regulatory/metabolismABSTRACT
BACKGROUND: It has recently been shown that certain chemotherapeutic agents can improve host immune responses. The present study aimed to demonstrate the mechanism by which chemotherapeutic agents modify the tumor microenvironment and induce tumor-specific immune responses. METHODS: Three mouse cancer cell lines [CT26 mouse colon cancer cells, B16 melanoma cells and Lewis lung carcinoma (LLC)], 5 human carcinoma cell lines (human esophageal squamous cell carcinoma cell lines TE8 and HEC46 and the human pancreatic carcinoma cell lines PK-9, AsPC-1 and SUIT-2) and 5 chemotherapeutic agents [mitoxantrone (MIT), mitomycin C(MMC), 5-fluorouracil (5FU), camptothecin (CPT-11) and cisplatin (CDDP)] that are frequently used in a clinical setting for cancer treatment were utilized to investigate the surface expression level of calreticulin and HLA class I after exposure to chemotherapeutic agents. RESULTS: Increased calreticulin (CRT) expression on the surface of mouse cell lines and, moreover, increased surface expression levels of both CRT and HLA class I in all human cell lines were observed in cells treated by the chemotherapeutic agents as compared with non-treated cells. The surface expression level of CRT was significantly correlated with the HLA class I expression level in all human cell lines. CONCLUSIONS: In conclusion, chemotherapeutic drugs can improve the immunogenicity of cancer cells in a cell-specific manner through the mechanism of translocation of CRT.
