Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal.
Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), 4200-135 Porto, Portugal.
Int J Mol Sci. 2021 Sep 10;22(18):9791. doi: 10.3390/ijms22189791.
The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma-carcinoma sequence (ACS).
We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic).
The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones.
The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.
肿瘤免疫微环境对肿瘤的发生和发展起着关键作用。本研究旨在分析散发性和家族性腺瘤性息肉病（FAP）病变在结直肠腺瘤-癌序列（ACS）中的免疫背景。
我们分析了 59 例 FAP 和 74 例散发性结直肠病变的免疫细胞计数（CD3+、CD4+、CD8+、Foxp3+和 CD57+）、肿瘤突变负担（TMB）、MHC-I 表达和 PD-L1 表达，包括低级别异型增生（LGD）的腺瘤（30 例 FAP；30 例散发性）、高级别异型增生的腺瘤（22 例 FAP；30 例散发性）和浸润性腺癌（7 例 FAP；14 例散发性）。
散发性结直肠 ACS 的特征是（1）免疫细胞计数逐渐减少，（2）TMB 和 MHC-I 表达增加，（3）PD-L1 表达降低。在 FAP 病变中，我们观察到了相同的模式，除了 TMB 在 ACS 中增加。FAP LGD 病变的 Foxp3+T 细胞计数低于散发性 LGD 病变。与散发性病变相比，FAP 病变的 PD-L1 表达下降更早发生。
结直肠 ACS 的特征是适应性免疫浸润的逐渐丧失，并建立了一个逐渐免疫冷的微环境。这些变化似乎与肿瘤细胞免疫原性的丧失或免疫抑制性肿瘤微环境的发生无关。
