In this model as well as in a syngeneic mouse skin SCC model we could demonstrate that the recruitment of Gr-1+ cells into the malignant stroma precedes persistent angiogenesis. We were able to show that CD11b+/Gr1+ immature myeloid Wee1 inhibitor cells constitute the majority of the tumor associated inflammatory infiltrate in SCCs of both immunocompetent C57Bl/6 and athymic nude mice.
In athymic nude mice depletion of Gr-1+ cells strongly inhibited tumor growth, angiogenesis and invasion. Interestingly, the depletion of Gr-1+ cells correlates with the reduction of MMP-9 in the malignant stroma. These findings imply that CD11b+/Gr-1+ cells have a tumor supporting role other than being suppressors of an anti-tumor T-cell response. Our current work focuses on the characterization of the functional contribution of Gr-1+ cells to tumor progression and identifies the factors that activate Gr-1+ cells within the tumor microenvironment. O18 Role of Inflammation and Immune GDC-0068 datasheet Privilege Microenvironment in Tumor Development Catherine Sautès-Fridman 1 , Isabelle Cremer1, Sylvain Fisson1, Wolf H. Fridman1 1 Department of Immunology, Cancer and Inflammation, Cordeliers Research Center, Paris, France Lung cancer develops at the mucosal airway interface. The respiratory epithelium is in contact
with the outside environment and exposed continuously to a broad range of pathogen agents including viruses. We describe the expression ID-8 of TLRs see more in human lung tumor cells (Non Small Cell Lung Carcinoma) and show that the stimulation by TLR7 and TLR8 agonists leads to increased tumor cell survival and chemoresistance. Transcriptional analysis suggests a TLR chronic stimulation of tumor cells in situ. These data indicate that TLR signaling during infection could directly favour tumor development. Primary intraocular lymphoma (PIOL) is a high grade
non-Hodgkin lymphoma which develops in an immunoprivileged site. Using a murine model of intraocular B cell lymphoma we detect an impaired Th1-Tc1 profile and Th17 cells in the eye concomitant to a high proportion of CD4+CD25+Foxp3+ T-cells. Systemic depletion of naturally occurring regulatory T cells induces only a slight decrease of the tumor burden suggesting that nTregs is one of the immune suppressive mechanisms occurring in this microenvironment. Other immune privilege mechanisms are under study. O19 Interaction of CTLs with Stroma Components: Endothelial Cell Cross-Recognition by Specific CTL and Influence of Hypoxic Stress Salem Chouaib 1 , Houssem Benlalam1, Muhammed Zaeem N.1 1 Institut Gustave Roussy, Villejuif, France Cellular interactions in the tumor stroma play a major role in cancer progression but can also induce tumor rejection.