Biography: Dr. Hatfield’s laboratory focuses on the role of hypoxia and immunosuppressive A2A adenosine receptor (A2AR) signaling in cancer and infectious disease. Through pharmacological and gene-targeting approaches, these studies aim to further our understanding of the tumor-protecting mechanisms that lead to immune evasion. This has led to the current understanding that tumor hypoxia and subsequent accumulation of extracellular adenosine represent a major biochemical barrier (hypoxia-adenosinergic suppression) that prevents immune-mediated tumor elimination.

Dr. Hatfield’s studies have implicated the blockade of A2AR as a feasible and translatable approach to improve cancer immunotherapies, including immune checkpoint inhibitors and CAR-T cell therapy. This is supported by promising results from recent clinical studies using A2AR antagonists for treatment of several forms of cancers. More recently, his lab has developed a multifaceted approach to genetically engineer ‘off the shelf’ CAR-T cells resistant to both biochemical and immunological inhibitory barriers. Using novel engineering strategies, his lab has generated CAR-T cells resistant to a diverse TME, unlocking the therapeutic potential of CAR-T cells against solid tumors. 

Dr. Hatfield’s research also demonstrated the immune-enhancing effects of tumor oxygenation. These studies uncovered the molecular mechanisms of the therapeutic reversal of tumor hypoxia. Oxygenation reprograms the TME and improves anti-tumor responses, justifying the use of supplemental oxygen and oxygenation agents as immunological co-adjuvants to combine with cancer immunotherapies. The impact of these studies was reflected by subsequent editorials and commentaries in peer reviewed journals (e.g. Cancer Cell, Nature Reviews Cancer) and press releases in major media outlets. More recently, his lab has focused on the next stage of this research by repurposing oxygenation agents (e.g. perfluorocarbon nano-emulsions) and blood substitutes for cancer immunotherapy. Dr. Hatfield’s research has demonstrated that combination of oxygen carrying nanoemulsions and respiratory hyperoxia synergize to alleviate tumor hypoxia-induced suppression and promote anti-tumor immune responses.