ABSTRACT
BACKGROUND: The signal transducer and activator of transcription 3 (STAT-3) is frequently overexpressed in cancer cells, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. The presence of phosphorylated STAT-3 (p-STAT-3) in the tumor can induce p-STAT-3 in tumor-associated immune cells that can return to the circulatory system. We hypothesized that the number of peripheral blood mononuclear cells (PBMCs) displaying p-STAT-3 would be increased in glioma patients, which would correlate with the extent of tumor-expressed p-STAT-3, and that higher p-STAT-3 levels in peripheral blood would correlate with a higher fraction of immune-suppressive regulatory T cells (Tregs). METHODS: We measured the percentage of PBMCs displaying p-STAT-3 in 19 healthy donors and 45 patients with primary brain tumors. The level of p-STAT-3 in tumor tissue was determined by immunohistochemistry. The degree of immune suppression was determined based on the fraction of Tregs in the CD4 compartment. RESULTS: Healthy donors had 4.8 +/- 3.6% of PBMCs that expressed p-STAT-3, while the mean proportion of PBMCs displaying p-STAT-3 in patients with GBM was 11.8 +/- 13.5% (P = 0.03). We did not observe a correlation by Spearman correlation between the degree of p-STAT-3 levels in the tumor and the percent of PBMCs displaying p-STAT-3. Furthermore, the percent of PBMCs displaying p-STAT-3 in glioma patients was not directly correlated with the fraction of Tregs in the CD4 compartment. CONCLUSION: We conclude that the percent of PBMCs displaying p-STAT-3 may be increased in malignant glioma patients.
Subject(s)
Brain Neoplasms/blood , Glioma/blood , Leukocytes, Mononuclear/metabolism , STAT3 Transcription Factor/blood , Adult , Aged , Brain Neoplasms/immunology , CD4-Positive T-Lymphocytes/metabolism , Female , Glioma/immunology , Humans , Male , Middle Aged , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Regulatory/metabolismABSTRACT
Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell count, specifically the CD4 and CD8 counts, there was no cumulative decline in the patient described in this case report. Depriving patients of this agent, in order to treat with immunotherapy, is controversial. Despite conventional dogma, we demonstrated that chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide-induced lymphopenia may prove to be synergistic with a peptide vaccine secondary to inhibition of regulatory T cells or their delayed recovery.
