Mye-EUNITER
 

Serre, Karine

It is well established that innate and adaptive cells of the immune system have anti-tumour properties, and that high frequency of tumour-infiltrating cytotoxic immune cells is associated with good prognosis. Our laboratory, and others, have shown that one of the major contributors to cancer immune surveillance are the innate-like gd T cells which are endowed with potent cytotoxic properties and the ability to rapidly provide anti-tumour cytokines such as IFN-g and TNF-a (Lanca et al., 2013). However, a major obstacle to cancer immunotherapy is the ability of tumours to recruit immune suppressive populations, which can be of myeloid origin, such as myeloid derived suppressor cells (MDSC), tumour associated macrophages (TAM) or neutrophils (TAN).

Models available:

gd T cells, deciphering the dynamic crosstalk between myeloid immunosuppressive cells and lymphoid protective murine effectors in cancer

Cells available:

I recently observed that gd T cells are impaired to respond to the B16-F0 tumour challenge when administrated intra-peritoneally. Interestingly, I found that in these tumour-bearing mice PMN-MDSC (CD11b+ Ly6G+ Ly6Clow) markedly infiltrated the peritoneal cavity, but not the subcutaneous site. This strongly highlights that the mechanisms employed by the cancer cells to escape the immune response are highly dependent on the tumour microenvironment. Moreover, this led-me to hypothesize that, under certain circumstances, gd T cells can be targeted and actively immunosuppressed by MDSC. Consistent with my hypothesis, depletion of PMN-MDSC with injection of anti-Gr1 Ab restores gd T cell tumour response.

I am currently leading a line of research, newly established in the laboratory of Professor Silva-Santos, that characterizes MDSC-dependent mechanism(s) of gd T cell immune suppression. This work may reveal novel insight into the tumour microenvironment features that regulate the fate of protective innate-like cytotoxic immune cells. One of my goals is to manipulate myeloid and lymphoid effector interplay in order to limit tumour growth. Ultimately, I anticipate that my studies inspire new avenues for the design of novel cancer immunotherapies and provide long-term clinical benefits.

Technology available:

Transplantation of tumour cells (B16-F0 melanoma cell line). Importantly, I soon would like to bring chemically induced murine tumour models.
Genetically deficient mouse models in selective cell populations.
Myeloid cell depletion (anti-Gr1 mAb).
Chemotherapeutic treatments. 
Flow cytometry analysis of myeloid regulatory cells.
Characterisation of myeloid compartment in tumour microenvironment and vicinity.
Assessment of inflammatory cytokine production (IFNg, IL-17).
Tumour growth by caliper measurement, or luciferase activity, or GFP expression.
In vitro characterization of the mechanisms of immunosuppression (on T cells) used by myeloid suppressor cells.

Key publications related to Mye-EUNITER:

1. N. Schmolka#, K. Serre#, A.R Grosso, M. Rei, D.J. Pennington, A. Gomez and B. Silva-Santos. “Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory γδ T cell subsets” Nature Immunology (2013) 14: 1093–1100. # contributed equally to this work.
2. E. Mohr, K. Serre, R.A. Manz, A.F. Cunningham, M. Khan, D.L. Hardie, R. Bird, and I.C.M. MacLennan. “Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature.” J Immunol (2009) 182:2113-2123
3. P. Machy, K. Serre, M. Baillet, and L. Leserman. “Induction of MHC class I presentation of exogenous antigen by dendritic cells is controlled by CD4+ T cells engaging class II molecules in cholesterol-rich domains.” J Immunol (2002) 168:1172-1180
4. P. Machy, K. Serre, and L. Leserman. “Class I-restricted presentation of exogenous antigen acquired by Fcgamma receptor-mediated endocytosis is regulated in dendritic cells.” Eur J Immunol (2000) 30:848-857
5. K. Serre , P. Machy, J.C. Grivel, G. Jolly, N. Brun, J. Barbet, and L. Leserman. “Efficient presentation of multivalent antigens targeted to various cell surface molecules of dendritic cells and surface Ig of antigen-specific B cells.” J Immunol (1998) 161:6059-6067

Contact details:

Instituto de Medicina Molecular
Faculdade de Medicina da Universidade de Lisboa
Avenida Professor Egas Moniz 1649-028 Lisboa
Portugal
(+351) 217 999 411
karine@kserre.net