title: Effects of conventional therapeutic interventions on the number and function of regulatory T cells.
abstract: Several lines of investigation have revealed the apparent interplay between the immune system of the host and many conventional, "standard-of-care" anticancer therapies, including chemotherapy and small molecule targeted therapeutics. In particular, preclinical and clinical studies have demonstrated the important role of regulatory T cells (Tregs) in inhibiting immune responses elicited by immunotherapeutic regimens such as those based on anticancer vaccines or checkpoint inhibitors. However, how the number and immunosuppressive function of Tregs change in cancer patients undergoing treatment with non-immune anticancer therapies remains to be precisely elucidated. To determine whether immunostimulatory therapies can be employed successfully in combination with conventional anticancer regimens, we have investigated both the number and function of Tregs obtained from the peripheral blood of carcinoma patients before the initiation and during the course of chemotherapeutic and targeted agent regimens. Our studies show that the treatment of breast cancer patients with tamoxifen plus leuprolide, a gonadotropin releasing hormone agonist, has minimal effects on Tregs, while sunitinib appears to exert differential effects on Tregs among patients with metastatic renal carcinoma. However, the administration of docetaxel to patients with metastatic prostate or breast cancer, as well as that of cisplatin plus vinorelbine to non-small cell lung cancer patients, appears to significantly increase the ratio between effector T cells and Tregs and to reduce the immunosuppressive activity of the latter in the majority of patients. These studies provide the rationale for the selective use of active immunotherapy regimens in combination with specific standard-of-care therapies to achieve the most beneficial clinical outcome among carcinoma patients.
authors.affiliation: Medical Oncology; Department of Internal Medicine; Tor Vergata University Clinical Center; University of Rome Tor Vergata; Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.affiliation: Medical Oncology; Department of Internal Medicine; Tor Vergata University Clinical Center; University of Rome Tor Vergata; Rome, Italy.
authors.forename: Vittore
authors.initials: V
authors.lastname: Cereda
authors.affiliation: Interinstitutional Multidisciplinary Biobank (BioBIM); Department of Laboratory Medicine and Advanced Biotechnologies; IRCCS San Raffaele Pisana; Rome, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: di Bari
authors.affiliation: Medical Oncology; Department of Internal Medicine; Tor Vergata University Clinical Center; University of Rome Tor Vergata; Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Formica
authors.affiliation: Interinstitutional Multidisciplinary Biobank (BioBIM); Department of Laboratory Medicine and Advanced Biotechnologies; IRCCS San Raffaele Pisana; Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Spila
authors.affiliation: Laboratory of Tumor Immunology and Biology; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.affiliation: Laboratory of Tumor Immunology and Biology; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Farsaci
authors.affiliation: Laboratory of Tumor Immunology and Biology; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Donahue
authors.affiliation: Laboratory of Tumor Immunology and Biology; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA ; Medical Oncology Branch; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.affiliation: Laboratory of Tumor Immunology and Biology; Center for Cancer Research; National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.affiliation: Interinstitutional Multidisciplinary Biobank (BioBIM); Department of Laboratory Medicine and Advanced Biotechnologies; IRCCS San Raffaele Pisana; Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
keywords: T lymphocytes; Tregs; carcinoma; chemotherapy; drug therapy