Long-chain polyunsaturated lipids associated with responsiveness to anti-PD-1 therapy are colocalized with immune infiltrates in the tumor microenvironment.
Long-chain polyunsaturated lipids associated with responsiveness to anti-PD-1 therapy are colocalized with immune infiltrates in the tumor microenvironment.
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与抗pd -1治疗反应性相关的长链多不饱和脂质与肿瘤微环境中的免疫浸润共定位。
DOI：
10.1016/j.jbc.2023.102902
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发表时间：
2023-03
影响因子：
4.8
通讯作者：
Eberlin, Livia S.
中科院分区：
文献类型：
--
作者：
King, Mary E.;Yuan, Robert;Chen, Jeremy;Pradhan, Komal;Sariol, Isabel;Li, Shirley;Chakraborty, Ashish;Ekpenyong, Oscar;Yearley, Jennifer H.;Wong, Janica C.;Zuniga, Luis;Tomazela, Daniela;Beaumont, Maribel;Han, Jin-Hwan;Eberlin, Livia S.
程序性细胞死亡蛋白-1（PD-1）在抗原特异性耗竭T细胞表面高度表达，与其配体PD-L1相互作用后，可导致免疫应答抑制。抗PD-1治疗已被证明可以延长多种癌症的生存期并产生持久的反应，但只有一部分患者从这种治疗中受益。尽管癌症免疫治疗后代谢改变的含义，抗肿瘤反应和代谢变化之间的机制联系仍然不清楚。在这里，我们使用解吸电喷雾电离质谱成像来检查来自三个同系小鼠模型的肿瘤组织的脂质谱，这些小鼠模型在基线和抗PD-1治疗后的三个时间点具有不同的治疗敏感性。这些成像实验揭示了与治疗反应程度相关的脂质谱的特定变化，并使我们能够确定抗PD-1治疗后反应性肿瘤中长链多不饱和脂质的显著增加。肿瘤组织的免疫荧光成像也表明，与治疗反应相关的脂质谱改变定位于肿瘤免疫浸润的致密区域。总体而言，这些结果表明，有效的抗PD-1治疗调节肿瘤免疫浸润中的脂质代谢，因此我们建议进一步研究相关的免疫代谢途径可能有助于更好地了解抗PD-1治疗的成功和失败。
The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with varying treatment sensitivity at the baseline and at three time points post-anti-PD-1 therapy. These imaging experiments revealed specific alterations in the lipid profiles associated with the degree of response to treatment and allowed us to identify a significant increase of long-chain polyunsaturated lipids within responsive tumors following anti-PD-1 therapy. Immunofluorescence imaging of tumor tissues also demonstrated that the altered lipid profile associated with treatment response is localized to dense regions of tumor immune infiltrates. Overall, these results indicate that effective anti-PD-1 therapy modulates lipid metabolism in tumor immune infiltrates, and we thereby propose that further investigation of the related immune-metabolic pathways may be useful for better understanding success and failure of anti-PD-1 therapy.
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影响因子：
8
作者：
Fransen, Marieke F.;Schoonderwoerd, Mark;Ossendorp, Ferry
通讯作者：
Ossendorp, Ferry
DOI：
10.1073/pnas.1408129111
发表时间：
2014-10-21
影响因子：
11.1
作者：
Calligaris, David;Caragacianu, Diana;Agar, Nathalie Y. R.
通讯作者：
Agar, Nathalie Y. R.
影响因子：
13.8
作者：
Claypool, Steven M.;Koehler, Carla M.
通讯作者：
Koehler, Carla M.
影响因子：
3.2
作者：
Eberlin, Livia S.;Ferreira, Christina R.;Dill, Allison L.;Ifa, Demian R.;Cheng, Liang;Cooks, R. Graham
通讯作者：
Cooks, R. Graham
晚期黑色素瘤中尼伐单抗加伊匹单抗或单用尼伐单抗与单用伊匹单抗的比较（CheckMate 067）： 多中心、随机、3 期试验的 4 年结果
影响因子：
51.1
作者：
Hodi, Frank Stephen;Chiarion-Sileni, Vanna;Wolchok, Jedd D.
通讯作者：
Wolchok, Jedd D.