文献类型：期刊文献

英文题名：Breaking the immune desert: Strategies for overcoming the immunological challenges of pancreatic cancer

作者：Wang, Tianming[1,2];Song, Wenjing[1];Tang, Yuan[1];Yi, Jianfeng[1];Pan, Haibang[1]

第一作者：Wang, Tianming

通信作者：Yi, JF[1];Pan, HB[1]

机构：[1]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou 730000, Gansu, Peoples R China;[2]Zhengning Cty Community Hlth Serv Ctr, Qingyang 745300, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：1880

期号：4

外文期刊名：BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

收录：;Scopus(收录号：2-s2.0-105005939944);WOS:【SCI-EXPANDED(收录号:WOS:001501717100001)】；

基金：The project was supported by the Natural Science Foundation of Gansu Province (21JR11RA160) , the Department of Finance of Gansu Province (BH2012-021) , and the Universities Innovation Fund of Gansu Province (2023S-76) .

语种：英文

外文关键词：Pancreatic cancer; Immune microenvironment; Immunotherapy; Metabolic intervention; Fibrotic matrix

摘要：Pancreatic cancer is characterised by its highly aggressive nature and extremely poor prognosis, with a uniquely complex tumour immune microenvironment that manifests as a prototypical "immune desert." This immunedesert phenotype primarily arises from the inherently low immunogenicity of the tumour, the formation of a dense fibrotic stroma, severe deficiency in immune cell infiltration, and profound immunosuppressive effects of the metabolic landscape. Specifically, dysregulated tryptophan metabolism, such as indoleamine 2,3-dioxygenase (IDO)-mediated catabolism, and excessive lactate accumulation contribute to impaired T-cell functionality. Collectively, these factors severely limit the efficacy of current immunotherapy strategies, particularly those based on immune checkpoint inhibitors, which have demonstrated significantly lower clinical response rates in pancreatic cancer than in other malignancies. In response to these therapeutic challenges, this review explores integrated treatment strategies that combine metabolic reprogramming, tumour microenvironment remodelling, and next-generation immune checkpoint blockades, such as LAG-3, TIM-3, and VISTA. These emerging approaches hold substantial promise for clinical application. For example, targeting key metabolic pathways, including glycolysis (Warburg effect) and glutamine metabolism, may help restore T-cell activity by alleviating metabolic stress within the tumour milieu. Additionally, localised administration of immune stimulators such as interleukin-12 (IL-12) and CD40 agonists may enhance immune cell infiltration and promote tumour-specific immune activation. Future research should prioritise large-scale, multicentre clinical trials to validate the therapeutic efficacy of these innovative strategies, aiming to achieve meaningful breakthroughs in pancreatic cancer immunotherapy and significantly improve long-term survival and clinical outcomes in affected patients.