Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 7008558, Japan.
Department of Pathology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Cancer Chemother Pharmacol. 2020 Jul;86(1):55-63. doi: 10.1007/s00280-020-04092-2. Epub 2020 Jun 12.
Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer.
We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen.
There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08).
Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study.
二甲双胍可能具有降低癌症风险的作用。然而，二甲双胍对癌症治疗的积极影响的作用机制尚不清楚。我们进行了一项前瞻性研究，以评估早期乳腺癌患者术前使用二甲双胍的效果。
我们通过比较术前获得的核心针活检（CNB）与手术标本，评估免疫因子（TILs、CD4+、CD8+、PD-L1、IFNγ和 IL-2）的影响。这项前瞻性研究于 2016 年 1 月至 12 月期间纳入了 17 名患者。我们还分析了同期接受手术的 59 名患者，以揭示 CNB 和手术标本之间免疫因子的相关性。
在 TILs 和 CD8+淋巴细胞方面，CNB 与手术标本之间存在中度相关性（TILs Rs=0.63，CD4+Rs=0.224，CD8+Rs=0.42）。在二甲双胍组中，5 名（29%）患者的 TILs 增加，2 名（12%）患者的 TILs 减少。在手术标本中，TILs 表达的 CD4+和 CD8+分别增加了 41%和 18%。然而，TILs 数量（p=0.0554）、CD4+（p=0.0613）和 CD8+（p=0.0646）的表达并没有显著增加。此外，IFNγ 的表达似乎因二甲双胍而增加（p=0.08）。
术前使用二甲双胍可能会增加 TILs 以及 CD4 和 CD8 阳性淋巴细胞的数量和 IFNγ 水平。根据这项初步研究的结果，二甲双胍可能会改善免疫功能，并有增加化疗敏感性和提高免疫疗法效果的可能性。
