Functional and Molecular Characterization of Myeloid Suppressor Cells Expanded During Lymphoma Tumour Progression

We previously reported that in mice with large progressing T-cell lymphoma tumours, dysfunctions in the antitumour CTL activity occur, associated with an accumulation of splenic arginase-producing myeloid suppressor cells (MSCs). In this study, we first demonstrate that both the presence and the activation state of these MSC depends on tumour evolution. While in tumour regressors hardly any arginase-producing MSC can be found, both the amount and the arginase activity of this population expands from early over late progressors. This gradual induction of MSCs is paralleled by an increasing suppression of CTL activity and Th1, but not Th2, cytokine production. Upon analysing the molecular repertoire of MSC in vitro, we found, besides arginase1, a well-established marker for alternatively activated myeloid cells or M2, a strong upregulation of FIZZ1 and Ym, two additional recently identified markers for M2. Further evaluation of molecular markers by microarray analysis in MSC yielded genes involved in wound healing (e.g. coagulation factor XIIIa), anti-inflammation (e.g. selenoprotein P), immunomodulation (e.g. PD-L2) and fat and sugar metabolism (e.g. leptin receptor). Of note, many of these genes are regulated by type 2 cytokines (IL-4, IL-13 and IL-10) and are therefore rather M2 associated. Overall, our data provide new markers for MSC in cancer and further establish their M2 activation state.