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Published: 18 June 2012
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
Abstract:
Ovarian
cancer is the leading cause of death from gynaecological malignancy.
Despite improved detection and treatment options, relapse rates remain
high. Combining immunotherapy with the current standard treatments may
provide an improved prognosis, however, little is known about how
standard chemotherapy affects immune potential (particularly T cells)
over time, and hence, when to optimally combine it with immunotherapy
(e.g., vaccines). Herein, we assess the frequency and ratio of CD8+
central memory and effector T cells as well as CD4+ effector and
regulatory T cells (Tregs) during the first 18 weeks of standard
chemotherapy for ovarian cancer patients. In this pilot study, we
observed increased levels of recently activated Tregs with tumor
migrating ability (CD4+CD25hiFoxp3+CD127−CCR4+CD38+ cells) in
patients when compared to controls. Although frequency changes of Tregs
as well as the ratio of effector T cells to Tregs were observed during
treatment, the Tregs consistently returned to pre-chemotherapy levels at
the end of treatment.
These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients.
These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients.
Keywords: CD4+ T cells; CD8 T cells; regulatory T cells; ovarian cancer
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