THC May Weaken the Immune System's Ability to Fight Cancer, Mouse Study Finds | Research

The takeaway

In mouse cancer models, THC reduced the effectiveness of PD-1 immunotherapy by suppressing T-cell function through the CB2 receptor, and higher levels of the endocannabinoid anandamide in human cancer patients were associated with worse survival.

Cancer patients using cannabis, oncologists, and researchers studying cannabinoid effects on immune function

THC reduced immunotherapy efficacy

What the researchers found

THC reduced the therapeutic effect of PD-1 checkpoint blockade in tumor-bearing mice. The endocannabinoid anandamide also impaired antitumor immunity. Using a knock-in mouse model, researchers found CNR2 (CB2 receptor) binds to JAK1 and inhibits downstream STAT signaling in T cells, suppressing their cancer-fighting function. In human cancer patients, higher serum anandamide levels correlated with poorer overall survival.

Why it matters

Many cancer patients use cannabis to manage chemotherapy side effects like nausea, often while receiving immunotherapy. This study raises the concern that THC could undermine the very treatment intended to fight their cancer.

The numbers in context

THC reduced PD-1 blockade therapeutic effect in mice; CNR2 binds JAK1 and inhibits STAT signaling; high serum anandamide associated with poor overall survival in human cancer patients

How the study worked

Preclinical study using multiple mouse tumor models. Tested THC and anandamide effects on PD-1 immunotherapy efficacy. Generated FLAG-tagged Cnr2 knock-in mice to study molecular mechanisms. Measured JAK/STAT signaling in T cells. Analyzed serum anandamide levels in human cancer patient cohort for survival association.

What this study cannot tell us

Mouse tumor models do not perfectly replicate human cancer immunology. The human survival data is observational and cannot prove anandamide caused worse outcomes. THC doses in mice may not reflect typical human cannabis use patterns. Study focused on CB2 mechanism but other pathways may also be involved.

How to read the evidence

Strong mechanistic evidence from multiple mouse models with supporting human observational data, published in a high-impact journal

When this study was published

2022 study

The bigger picture

Immunotherapy has transformed cancer treatment, but not all patients respond. If cannabinoids suppress the immune response that immunotherapy is trying to boost, this could partly explain treatment failures in cannabis-using patients and would have major implications for supportive care guidelines.

Questions still open

Should cancer patients receiving immunotherapy avoid cannabis? Would CBD (which has different receptor interactions) also suppress antitumor immunity? At what THC exposure level does immunosuppression become clinically relevant?

Common questions

Should cancer patients stop using cannabis during immunotherapy?

This study raises that concern but cannot definitively answer the question for humans. The mouse data showed THC reduced immunotherapy effectiveness, and human data showed an association between endocannabinoid levels and survival, but clinical trials in humans are needed.

Does CBD have the same effect on cancer immunity?

This study did not test CBD. The immunosuppressive mechanism operated through the CB2 receptor and THC specifically. CBD has different receptor interactions, so its effects may differ, but this was not examined here.

Read the original research

Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2.

Signal transduction and targeted therapy, 7(1), 99

View on PubMed ↗Publisher’s paper ↗

Citation

Xiong, Xinxin; Chen, Siyu; Shen, Jianfei; You, Hua; Yang, Han; Yan, Chao; Fang, Ziqian; Zhang, Jianeng; Cai, Xiuyu; Dong, Xingjun; Kang, Tiebang; Li, Wende; Zhou, Penghui. (2022). Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2.. Signal transduction and targeted therapy, 7(1), 99. https://doi.org/10.1038/s41392-022-00918-y