补充L-精氨酸可增强抗癌化学免疫治疗的疗效。,Cancer Science

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补充L-精氨酸可增强抗癌化学免疫治疗的疗效。
Cancer Science ( IF 4.5 ) Pub Date : 2020-05-19 , DOI: 10.1111/cas.14490
Yusuke Satoh ₁ , Hitoshi Kotani ₁ , Yuichi Iida ₁ , Takahito Taniura ₂ , Yoshitomo Notsu ₃ , Mamoru Harada ₁

Affiliation

髓样来源的抑制细胞（MDSC）在荷瘤宿主的免疫抑制中起关键作用。MDSC表达精氨酸酶I和吲哚胺2,3-二加氧酶; 它们通过分别降低l-精氨酸和l-色氨酸的水平来抑制T细胞功能。我们检查了补充这些氨基酸对CT26结肠癌小鼠的抗癌作用。的口服补充升精氨酸或升-色氨酸（30毫克/小鼠）不影响肿瘤的生长，而的口服补充d精氨酸是致命的。l的补充精氨酸显示出增强环磷酰胺（CP）功效的趋势。CP降低了携带CT26的小鼠的脾脏和肿瘤组织中粒细胞MDSC的比例，并增加了单核MDSC的比例。l单独添加精氨酸不会影响MDSC子集。CP治疗倾向于降低携带CT26的小鼠的l-精氨酸的血浆水平，并显着增加肿瘤浸润的CD8 ⁺ T细胞的数量。此外，补充l-精氨酸可显着增加引流淋巴结中肿瘤肽特异性CD8 ⁺ T细胞的比例。重要的是，对l的补充精氨酸显着增加了用CP和抗PD-1抗体治疗的治愈小鼠的数量。完全，升精氨酸补充节目承诺为促进化学免疫疗法的治疗效果。

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Supplementation of l-arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy.

Myeloid‐derived suppressor cells (MDSCs) play a crucial role in immunosuppression in tumor‐bearing hosts. MDSCs express arginase‐I and indoleamine 2,3‐dioxygenase; they suppress T‐cell function by reducing the levels of l ‐arginine and l ‐tryptophan, respectively. We examined the anticancer effects of supplementation of these amino acids in CT26 colon carcinoma‐bearing mice. Oral supplementation of l ‐arginine or l ‐tryptophan (30 mg/mouse) did not affect tumor growth, whereas oral supplementation of d ‐arginine was lethal. Supplementation of l ‐arginine showed a tendency to augment the efficacy of cyclophosphamide (CP). CP reduced the proportions of granulocytic MDSCs and increased the proportions of monocytic MDSCs in the spleen and tumor tissues of CT26‐bearing mice. l ‐Arginine supplementation alone did not affect the MDSC subsets. CP treatment tended to reduce the plasma levels of l ‐arginine in CT26‐bearing mice and significantly increased the number of tumor‐infiltrating CD8⁺ T cells. In addition, l ‐arginine supplementation significantly increased the proportions of tumor peptide‐specific CD8⁺ T cells in draining lymph nodes. Importantly, additional supplementation of l ‐arginine significantly increased the number of cured mice that were treated with CP and anti‐PD‐1 antibody. Totally, l ‐arginine supplementation shows promise for boosting the therapeutic efficacy of chemoimmunotherapy.

更新日期：2020-07-28

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