Hypoxia and antitumor CD8+ T cells: An incompatible alliance?

T Lymphocytes face pathologically low O-2 tensions within the tumor bed at which they will have to function in order to impact on the malignancy. Recent studies highlighting the importance of O-2 and hypoxia-inducible factors for CD8(+) T-cell function and fate must now be integrated into tumor immunology concepts if immunotherapies are to progress. Here, we discuss, reinterpret, and reconcile the many apparent contradictions in these data and we propose that O-2 is a master regulator of the CD8(+) T-cell response. Certain T cell functions are enhanced, others suppressed, but on balance, hypoxia is globally detrimental to the antitumor response.