Attenuated XXXX Stimulates Immunity to @entity788 by Manipulation of Myeloid Cell Populations.

@entity788 @entity146 @entity5 @entity19 @entity3204
UNASSIGNED: Suppressive myeloid cells represent a significant barrier to the generation of productive antitumor immune responses to many solid @entity5 . Eliminating or reprogramming suppressive myeloid cells to abrogate @entity5 -associated immune suppression is a promising therapeutic approach. We asked whether treatment of @entity146 disseminated @entity788 with the immunotherapeutic attenuated @entity3204 vaccine strain CPS would trigger @entity5 -associated myeloid cells to generate therapeutic antitumor immune responses. CPS treatment significantly decreased @entity5 -associated macrophages and markedly increased @entity788 microenvironment. Tumor-resident macrophages and dendritic cells, particularly cells actively invaded by CPS, increased expression of costimulatory molecules CD80 and CD86 and concomitantly boosted their production of IL12. CPS treatment increased CD4(+) and CD8(+) T-cell infiltration into the @entity5 microenvironment, activated @entity5 -resident T cells, and increased IFNy production by T-cell populations. CPS treatment provided a significant therapeutic benefit in @entity788 -bearing @entity19 . This therapeutic benefit depended on IL12 and IFNy production, MyD88 signaling, and CD8(+) T-cell populations. Although CD4(+) T cells exhibited activated effector phenotypes and produced IFNy, CD4(+) T cells as well as natural killer cells were not required for the therapeutic benefit. In addition, CD8(+) T cells isolated from CPS-treated @entity5 -bearing @entity19 produced IFNy after re-exposure to @entity788 antigen, suggesting this immunotherapeutic treatment stimulated @entity5 cell antigen-specific CD8(+) T-cell responses. This work highlights the potency and immunotherapeutic efficacy of CPS treatment and demonstrates the significance of targeting @entity5 -associated myeloid cells as a mechanism to stimulate more effective immunity to @entity788 . Cancer Immunol Res; 3(8); 1-11.   2015 AACR.
