Abstract
The development of cancer has historically been attributed to genomic alterations of normal host cells. Accordingly, the aim of most traditional cancer therapies has been to destroy the transformed cells themselves. There is now widespread appreciation that the progressive growth and metastatic spread of cancer cells requires the cooperation of normal host cells (endothelial cells, fibroblasts, other mesenchymal cells, and immune cells), both local to, and at sites distant from, the site at which malignant transformation occurs. It is the balance of these cellular interactions that both determines the natural history of the cancer, and influences its response to therapy. This active tumor-host dynamic has stimulated interest in the tumor microenvironment as a key target for both cancer diagnosis and therapy. Recent data has demonstrated both that the presence of CD8+ T cells within a tumor is associated with a good prognosis, and that the eradication of all malignantly transformed cells within a tumor requires that the intra-tumoral concentration of cytolytically active CD8+ effector T cells remain above a critical concentration until every tumor cell has been killed. These findings have stimulated two initiatives in the field of cancer immunotherapy that focus on the tumor microenvironment. The first is the development of the immune score as part of the routine diagnostic and prognostic evaluation of human cancers, and the second is the development of combinatorial immune-based therapies that reduce tumor-associated immune suppression to unleash pre-existing or therapeutically-induced tumor immunity. In support of these efforts, the Society for the Immunotherapy of Cancer (SITC) is sponsoring a workshop entitled "Focus on the Target: The Tumor Microenvironment" to be held October 24-25, 2012 in Bethesda, Maryland. This meeting should support development of the immune score, and result in a position paper highlighting opportunities for the development of integrative cancer immunotherapies that sculpt the tumor microenvironment to promote definitive tumor rejection.
Highlights
Cancer therapies have largely focused on destroying the transformed cancer cell itself
Chemotherapy classically exerts an anti-tumor effect by selectively disrupting an aspect of tumor cell biology that gives malignant cells a relative growth advantage compared to normal cells
There is widespread appreciation that non-transformed host cells interact with malignant tumor cells to form a dynamic tumor microenvironment in which the non-transformed cells exert both positive and negative effects on the growth and spread of the cancer cells, and that these in turn affect the phenotype of the non-transformed host cells [2]
Summary
Cancer therapies have largely focused on destroying the transformed cancer cell itself. The immune score An immune score that quantifies the intra-tumoral location and density of CD8+ T cells and memory CD45RO + T cells has been proposed as a useful approach both for predicting the impact of the tumor microenvironment on clinical outcome in colon cancer patients, and possibly for selecting therapy [13]. Other factors within the tumor microenvironment are likely to influence the immune score, including other immune cells (intra-tumoral Treg, myeloid-derived suppressor cells, alternatively activated macrophages), stromal factors (fibroblasts, other mesenchymal cells, secretory products like tenascin [25]), and the integrity of the tumor cell genome Of these factors, intratumoral Treg are one variable that has been associated with poor prognosis in many solid tumors (ovarian, breast, and pancreatic cancers), but paradoxically with favorable prognosis in colon cancer [26]. The impact of epigenetic therapy on tumor immunity is an emerging area of investigation [47]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
