From Infancy to Young Adulthood The post Paget research of the TME was initiated by

two non-interacting groups of research pioneers: immunologists and scientists focusing on angiogenesis. Until the late seventies or early eighties, these two research groups performed by far the most significant TME research. Most of the early studies on the immune microenvironment of cancer focused on the characterization and functions of cellular and humoral immune components in the tumor microenvironment [11–36] These studies established that immunocytes including T cells [23, 32], B cells [14, 17], NK cells [24, 31] and macrophages [19, 20, 26, 27, 29, 33, 35, 36] have the capacity to infiltrate solid tumors in humans click here and in animals. Other studies demonstrated that immunoglobulins (Ig) and complement components could be detected in the microenvironment PF477736 in vivo of solid tumors. Tumor cells in humans, rats and mice were found to be coated with Ig [11, 12, 18, 25, 34]. This coat was composed either of anti tumor antibodies bound to the tumor cells via the antigen binding site (in an antibody-epitope interaction) [37] or of Ig (mainly IgG) bound to epithelial or mesenchymal tumor cells via Fc receptors (FcR) expressed by such tumor cells [38]. The tumor-associated FcR

was a promalignancy factor [39]. Microenvironmental factors were found to regulate the expression Edoxaban of the FcR expressed by the tumor cells [40]. The state of the art with respect to the immune microenvironment of cancer was evaluated by leading cancer immunologists in a UICC-supported workshop on “In-Situ Expressions of Tumor Immunity” that took place in 1978 in Tel Aviv, Israel. Some of the participants of the 1978 meeting participate also in the Versailles

Conference. The proceedings of the Tel Aviv meeting were published [41]. Most of the presentations dealt with the characterization of immune components (cells and molecules) found at the sites of solid tumors and on their functional activities. The bottom line of the workshop’s deliberations was that the immune components that localized in the TME were relatively deficient in anti tumor activities in comparison to similar components originating from systemic sites. Some tumor-localizing components, especially tumor-localizing antibodies even enhanced tumor development. The other group of TME pioneers led by Judah Folkman focused on angiogenesis. They realized very early that tumor selleck products proliferation was dependent upon blood supply and that the interactions of tumor and endothelial cells initiated and drove this process. Angiogenic factors were identified in various types of tumors and the possibility was raised that inhibiting such factors or their interaction with endothelial cells will be of clinical benefit to cancer patients [42–59].