Domblides Charlotte, Soubeyran Isabelle, Lartigue Lydia, Mahouche Isabelle, Lefort Félix, Velasco Valérie, Barnetche Thomas, Blanco Patrick, Déchanet-Merville Julie, Faustin Benjamin
ImmunoConcEpt Laboratory, CNRS UMR 5164, Bordeaux University, 33076 Bordeaux, France.
Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital-CHU, 33000 Bordeaux, France.
Cancers (Basel). 2020 Nov 24;12(12):3500. doi: 10.3390/cancers12123500.
(1) We wanted to assess the prognostic impact of inflammasomes involved in gut epithelial homeostasis and the development of human colorectal cancer (CRC). (2) We investigated the expression of inflammasome components in colonic epithelial cells at the protein level in patient tissues, through an immunofluorescence assay. (3) In a cohort of 104 patients, we found that all inflammasome components were downregulated in CRC. Loss of epithelial (but not stromal) expression of NLRP6, caspase-1 and IL-18 was associated with an increased mortality of 72%, 58% and 68% respectively and to disease progression into metastasis. The loss of epithelial and stromal IL-18 but not NLRP6, was associated to lower tumor immune infiltrates in the lymphoid compartment and higher Programmed cell Death receptor 1 (PD-1) expression. Finally, we found that combined downregulation of IL-18 and NLRP6 was associated with a worse outcome. Indeed, 5-year survival rates were 26% for the NLRP6low/IL-18low tumors, compared to 64.4% for the entire cohort. This downregulation was associated with a more advanced disease ( < 0.0001) and a trend to lower lymphoid cell infiltration. (4) We identified critical inflammasome markers that may help in better stratifying patients for prognosis in CRC and could help clinicians to determine which patients may benefit from immunotherapies.
(1) 我们想要评估参与肠道上皮稳态及人类结直肠癌（CRC）发生发展的炎性小体的预后影响。(2) 我们通过免疫荧光测定法，在患者组织中检测结肠上皮细胞中炎性小体成分的蛋白水平表达。(3) 在一个104名患者的队列中，我们发现所有炎性小体成分在CRC中均下调。NLRP6、半胱天冬酶 -1和白细胞介素 -18上皮（而非基质）表达的缺失分别与死亡率增加72%、58%和68%相关，并与疾病进展至转移有关。上皮和基质白细胞介素 -18而非NLRP6的缺失与淋巴区室中较低的肿瘤免疫浸润及较高的程序性细胞死亡受体1（PD -1）表达相关。最后，我们发现白细胞介素 -18和NLRP6的联合下调与更差的预后相关。确实，NLRP6低/白细胞介素 -18低的肿瘤5年生存率为26%，而整个队列的5年生存率为64.4%。这种下调与疾病进展更严重（<0.0001）及淋巴样细胞浸润降低的趋势相关。(4) 我们确定了关键的炎性小体标志物，这些标志物可能有助于更好地对CRC患者进行预后分层，并可帮助临床医生确定哪些患者可能从免疫治疗中获益。
