Use of acetaminophen (APAP) has been linked to weakened immunological responses to vaccinations. For a study, researchers evaluated the effect of APAP on the effectiveness of immunotherapy in cancer patients.
Plasma analysis was used to measure exposure to APAP and link it with clinical outcomes in 3 separate cohorts of patients with advanced cancer who received immune checkpoint blockers (ICBs). Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers and a preclinical tumor model were used to assess the immunomodulatory effects of APAP.
Independent of other prognostic markers, detectable plasma APAP levels at the start of treatment were linked to a significantly poorer clinical outcome in cancer patients receiving ICB. ICB effectiveness in the preclinical MC38 model and PD-1 blockade-related interferon-γ secretion by human PBMCs were both markedly decreased by APAP. Additionally, regulatory T cell (Tregs) infiltration into tumors was dramatically boosted when ICB effectiveness in vivo was reduced. Peripheral Tregs significantly expanded after receiving APAP over the course of 24 hours in healthy persons. Interleukin-10, a critical mediator of Treg-induced immune suppression, was also markedly elevated in cancer patients receiving APAP following ICB therapy.
In the study, the significance of APAP as a possible suppressor of antitumor immunity was well supported by preclinical and clinical data. As a result, APAP should only be administered with care to patients receiving ICB.