Metformin effects on FOXP3+ and CD8+ T cell infiltrates of head and neck squamous cell carcinoma

Metformin effects on FOXP3+ and CD8+ T cell infiltrates of head and neck squamous cell carcinoma:

Objectives

Alterations of cellular metabolism have been implicated in immune dysfunction in the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC). Metformin has recently emerged as a candidate of interest for combination with immunotherapy in HNSCC. This study investigated the effect of metformin on immune cell infiltrates of HNSCC.

Methods

Retrospective analysis of T cell infiltrates in primary tumor specimens from patients enrolled in a clinical window of opportunity trial of presurgical metformin. Metformin was titrated to a standard diabetic dose (2000 mg/day) for a minimum of 9 days (mean 13.6 days) prior to surgical resection. Pre and posttreatment surgical specimens from 36 patients (16 HPV⁺, 20 HPV⁻) were comparatively analyzed. FOXP3⁺ and CD8⁺ immune cell infiltrates in the tumor and peritumoral stroma of pre and posttreatment HNSCC specimens were quantified by digital image analysis using Visiopharm software.

Results

Metformin treatment was associated with a 41.4% decrease in FOXP3⁺ T cells in intratumor regions of interest (P = .004) and a 66.5% increase in stromal CD8⁺ T cells at the leading edge of the tumor (P = .021) when compared to pretreatment biopsies. This was reflected in increased CD8⁺/FOXP3⁺ cell ratios within the tumor (P < .001) and stromal compartments (P < .001). The effects of metformin occurred independently of HPV status.

Conclusion

Metformin treatment may favorably alter the immune TME in HNSCC independent of HPV status.

Level of Evidence

1b. This study is most accurately described as a non‐randomized controlled trial and therefore may reflect a level of evidence below 1b but above 2a from the provided “levels of evidence” chart. Laryngoscope, 2019