title: The combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophagesin situ.
abstract: Tumor associated macrophages and tumor infiltrating regulatory T cells greatly hamper host-protective antitumor responses. Therefore, we utilized a novel immunomodulator, heat-killedMycobacterium indicus pranii(Mw), to repolarize TAM and an agonistic GITR antibody (DTA-1) to reduce intratumoral regulatory T cell frequency for generation of a host-protective antitumor response. Although, the combination ofMwand DTA-1was found to be effective against advanced stage tumors, however,Mwor DTA-1 failed to do so when administered individually. The presence of high level of regulatory T cells abrogated the onlyMwinduced antitumor functions, whereas only DTA-1 treatment was found to be ineffective due to its inability to induce TAM repolarizationin vivo.The combination therapy was found to be effective since DTA-1 treatment reduced the frequency of regulatory T cells to such an extent where they could not attenuateMwinduced TAM repolarizationin vivo.Therefore, the combination therapy involvingMwand DTA-1 may be utilized to the success of advanced stage solid tumor immunotherapies.
authors.affiliation: Division of Molecular Medicine; Bose Institute ; Kolkata, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Molecular Medicine; Bose Institute ; Kolkata, India.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Halder
authors.affiliation: Division of Molecular Medicine; Bose Institute ; Kolkata, India.
authors.forename: Sweta
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Division of Molecular Medicine; Bose Institute ; Kolkata, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.affiliation: Division of Molecular Medicine; Bose Institute ; Kolkata, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
keywords: APC, antigen presenting cell; DTA-1; IFN-γ receptor; IL, interleukin; LPS, lipopolysaccharide; MACS, magnetic-activated cell sorting; Mw; Mw, Mycobacterium indicus pranii; STAT, signal transducer and activator; TAM, tumor associated macrophages; antigen presentation; melanoma; regulatory T cells; tumor associated macrophages