Cyclooxygenase-2 (COX-2), the enzyme at the rate-limiting step of prostanoid production, has been found to be overexpressed in human lung cancer. To evaluate lung tumor COX-2 modulation of antitumor immunity, we studied the antitumor effect of specific genetic or pharmacological inhibition of COX-2 in a murine Lewis lung carcinoma (3LL) model. Inhibition of COX-2 led to marked lymphocytic infiltration of the tumor and reduced tumor growth. Treatment of mice with anti-PGE2 mAb replicated the growth reduction seen in tumor-bearing mice treated with COX-2 inhibitors. COX-2 inhibition was accompanied by a significant decrement in IL-10 and a concomitant restoration of IL-12 production by APCs. Because the COX-2 metabolite PGE2 is a potent inducer of IL-10, it was hypothesized that COX-2 inhibition led to antitumor responses by down-regulating production of this potent immunosuppressive cytokine. In support of this concept, transfer of IL-10 transgenic T lymphocytes that overexpress IL-10 under control of the IL-2 promoter reversed the COX-2 inhibitor-induced antitumor response. We conclude that abrogation of COX-2 expression promotes antitumor reactivity by restoring the balance of IL-10 and IL-12 in vivo.

Verastem. D.M.B. serves as consultant for, is a member of the scientific advisory board of, and institution is the site of a PI clinical trial (grant paid to the institution) from AbbVie and Genentech.

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Background Post-viral olfactory dysfunction is a common cause of both short- and long-term smell alteration. The coronavirus pandemic further highlights the importance of post-viral olfactory dysfunction. Currently, a comprehensive review of the neural mechanism underpinning post-viral olfactory dysfunction is lacking. Objectives To synthesize the existing primary literature related to olfactory dysfunction secondary to viral infection, detail the underlying pathophysiological mechanisms, highlight relevance for the current COVID-19 pandemic, and identify high impact areas of future research. Methods PubMed and Embase were searched to identify studies reporting primary scientific data on post-viral olfactory dysfunction. Results were supplemented by manual searches. Studies were categorized into animal and human studies for final analysis and summary. Results A total of 38 animal studies and 7 human studies met inclusion criteria and were analyzed. There was significant variability in study design, experimental model, and outcome measured. Viral effects on the olfactory system varies significantly based on viral substrain but generally include damage or alteration in components of the olfactory epithelium and/or the olfactory bulb. Conclusions The mechanism of post-viral olfactory dysfunction is highly complex, virus-dependent, and involves a combination of insults at multiple levels of the olfactory pathway. This will have important implications for future diagnostic and therapeutic developments for patients infected with COVID-19.