Abstract PO-089: Opioid-mediated suppression of anti-tumor immunity via peripheral OPRM1 signaling in head and neck squamous cell carcinoma
Bibliographic record
Abstract
Abstract Head and Neck squamous cell carcinoma (HNSCC) causes severe pain, beyond what is reported in other cancer types. Opioids are the current backbone of HNSCC pain treatment but may have an immunomodulatory effect in the presence of cancer; T cells express opioid receptors. We recently demonstrated that opioids may affect the efficacy of anti-PD1 monoclonal antibody (mAb) treatment in recurrent/metastastic HNSCC patients; opioid usage was associated with significantly lower progression free survival and overall survival as well as decreased CD8 T cells in the tumor microenvironment. We hypothesized that cancer immunosurveillance is impaired by the immunosuppressive actions of exogenous opioids via peripheral mu-opioid receptor (OPRM1) signaling. A syngeneic mouse oral cancer model was used to determine if analgesic morphine impacted the tumor-associated immune response during tumor progression and in response to anti-PD1 mAb; mouse oral cancer cell line 1 (MOC1) tumor-bearing mice were treated with vehicle or morphine (10mg/kg i.p., 2x daily for 4.5 days) and the tumor-associated immune infiltrate was assessed between groups using flow cytometry. Anti-PD1 mAb (250µg/mouse, 3 × 2 day interval) was initiated directly following morphine treatment. Co-administration of methylnaltrexone (MNTX), a peripheral OPRM1 antagonist used to confirm specificity and site of action of the morphine-induced effects. Finally, any direct effects of morphine on tumor cells were investigated in oral cancer cell lines using quantitative PCR and colorimetric proliferation assays. Morphine induced a 75±5% reduction in CD8+ T cells and a 90±3% reduction in CD19+ B cells in MOC1 compared to sham mice (n=6/group); morphine-induced immunosuppression was completely blocked with co-treatment of MNTX. Studies involving morphine administration prior to anti-PD1 treatment are currently underway but given the substantial suppression in infiltrating lymphocyte populations, efficacy is expected to be lessened. Lastly, Oprm1 expression was not detected at the mRNA level in mouse oral cancer cell lines. In vitro, 10µM morphine did not induce cell proliferation (proliferation relative to vehicle after 48hr; vehicle=100±8.3%, morphine=115.7±9.6%) or improve wound healing (wound closure after 24hr; vehicle=76.2±11.6%, morphine=78.5±11.4%). Taken together, our data suggest that morphine suppresses anti-tumor immunity via peripheral OPRM1 signaling in immune cells but not tumor cells. Further investigation is warranted to determine whether peripheral opioid blockade (i.e. MNTX) can slow tumor progression and improve response to cancer treatments while preserving centrally-mediated analgesia. Citation Format: Lisa A. McIlvried, Mona Yuan, Nicole L. Horan, Megan A. Atherton, Marci L. Nilsen, Dan P. Zandberg, Nicole N. Scheff. Opioid-mediated suppression of anti-tumor immunity via peripheral OPRM1 signaling in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-089.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".