Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

Published: 18 June 2012

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)

Download PDF Full-Text 

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+CD25^hiFoxp3+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.

phase 11/111 - Comparing Three Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov

Comparing Three Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer - Full Text View - ClinicalTrials.gov

Comparing Three Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

This study is currently recruiting participants.

Verified March 2012 by NCIC Clinical Trials Group

First Received on October 9, 2009.   Last Updated on March 9, 2012   History of Changes

Sponsor:	NCIC Clinical Trials Group
Collaborators:	National Cancer Institute (NCI) Grupo Español de Investigación en Cáncer de Ovario Cancer Research UK Southwestern Oncology Group (SWOG)
Information provided by (Responsible Party):	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00993655

  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating patients with ovarian epithelial cancer, primary peritoneal cancer, and fallopian tube cancer.

PURPOSE: This randomized phase II/III trial is comparing the side effects of three combination chemotherapy regimens and to see how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

Condition	Intervention	Phase
Fallopian Tube Cancer Metastatic Cancer Ovarian Cancer Peritoneal Cavity Cancer	Drug: carboplatin Drug: cisplatin Drug: paclitaxel Procedure: quality-of-life assessment	Phase II Phase III

Overcoming TRAIL resistance in ovarian carcinoma

CONCLUSION: Continued efforts with combination therapy designed to target multiple steps in apoptotic pathways may not only improve the efficacy of TRAIL-mediated therapies, but may also improve quality of life for ovarian cancer patients by reducing toxicity associated with cancer therapy.

Platinum-based adjuvant chemotherapy for early-stage ovarian cancer (abstract)

Conclusions
Combination therapy is administered more often than carboplatin; especially in those with younger age, better PS and nonmucinous histology. Recurrence and death rates were similar with both treatments. Well-designed trials are needed to identify the optimum chemotherapy regimen in this group.