Acetaminophen impacts efficacy of immunotherapy in cancer patients: Study

France: Acetaminophen (APAP) suppresses antitumor immunity in patients with advanced cancer, states an article published in Annals of Oncology. Hence, in patients treated with immune checkpoint blockers (ICB), APAP should be used with caution, the researchers suggest.

In cancer patients, pain is a highly prevalent and distressing symptom. Acetaminophen, a non-opioid analgesic is a first-line strategy to manage mild-to-moderate pain in patients with advanced cancer. It improves pain and well-being in these patients. Preclinical studies have illustrated that acetaminophen inhibits the proliferation of immune cells and the T cell-dependent antibody response. Additionally, randomized studies have reported a negative impact of acetaminophen on vaccination response, with decreased antibody levels in individuals receiving acetaminophen for fever prophylaxis."

A. Marabelle, University Paris-Saclay, Villejuif, France, and colleagues conducted a study to assess APAP's impact on immunotherapy efficacy in patients with cancer.

Researchers enrolled patients with advanced cancer who were treated with immune checkpoint blockers (ICB) for three independent cohorts. Exposure to APAP was assessed by plasma analysis and was correlated with clinical outcomes. APAP immunomodulatory effects were evaluated on pre-clinical tumor model and human peripheral blood mononuclear cells (PBMCs) from healthy donors.

Key findings of the study,

• Detectable plasma APAP levels at treatment onset were associated with a significantly worse clinical outcome in ICB-treated cancer patients, independent of other prognostic factors.

• APAP significantly reduced ICB efficacy in the pre-clinical MC38 model, as well as the production of PD1 blockade-related interferon-γ secretion by human PBMCs.

• Reduction of ICB efficacy in vivo was associated with significantly increased tumor infiltration by regulatory T cells (Tregs).

• Administration of APAP over 24h induced a significant expansion of peripheral Tregs in healthy individuals.

• In cancer patients taking APAP, Interleukin-10, a crucial mediator of Treg-induced immune suppression, was significantly upregulated upon treatment with ICB.

The authors conclude that the study provides strong pre-clinical and clinical evidence of the role of APAP as a potential suppressor of antitumor immunity. Hence, APAP should be used with caution in patients treated with ICB. Further research is needed to decipher the impact of acetaminophen on immunity.

Reference:

Bessede A, Marabelle A, Guégan JP, Danlos FX, Cousin S, Peyraud F, Chaput N, Spalato M, Roubaud G, Cabart M, Khettab M, Chaibi A, Rey C, Nafia I, Mahon FX, Soria JC, Italiano A. Impact of acetaminophen on the efficacy of immunotherapy in cancer patients. Ann Oncol. 2022 May 30:S0923-7534(22)01208-X. doi: 10.1016/j.annonc.2022.05.010. Epub ahead of print. PMID: 35654248.