Hypoxia: A Formidable Saboteur of the Anti-tumor Response

The tumor microenvironment (TME) promotes neoplastic transformation, supports tumor growth and invasion, protects the tumor from host immunity and fosters therapeutic resistance. It is well established that tumor stroma components are engaged in an active and complex molecular cross-talk that has serious implications for immunological recognition of tumor cells in shaping the microenvironment. In this regard, a common feature of solid tumors and one of the hallmarks of the TME is at present attracting a particular and increased attention in the field of cancer immunology since hypoxic stress impacts angiogenesis, tumor progression and immune tolerance. In this chapter, we will discuss how tumors use hypoxic stress to their own advantage by activating key biochemical and cellular pathways that are important in their progression and survival and how hypoxic stress induces tumor target adaptation that compromises the effectiveness of CTL activity. In this respect, modulating hypoxia may be a good strategy to control tumor progression at different fronts.