The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Autor: Fabiana Sousa, Sara Miranda, João Freitas, José Carlos Machado, Carlos Resende, Cecília Durães, Louisa Spaans, Manuela Baptista, José Luis Costa, Lídia Pinho, Diogo Garcia, Dina Leitão, Irene Gullo, Fátima Carneiro, Joana Reis
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
Male
CD3 Complex
Cell Count
Tumor initiation
Adaptive Immunity
CD8-Positive T-Lymphocytes
immunogenicity
PD-L1 expression
B7-H1 Antigen
CD57 Antigens
Tumor Microenvironment
Biology (General)
Spectroscopy
Aged
80 and over
colorectal adenoma
tumor immune microenvironment
FOXP3
Forkhead Transcription Factors
APC germline alterations
General Medicine
Middle Aged
Computer Science Applications
Gene Expression Regulation
Neoplastic
Chemistry
colorectal adenocarcinoma
Adenomatous Polyposis Coli
Colorectal Neoplasms
Adult
congenital
hereditary
and neonatal diseases and abnormalities
QH301-705.5
chemical and pharmacologic phenomena
Context (language use)
Colorectal adenoma
Adenocarcinoma
Article
Catalysis
Familial adenomatous polyposis
Inorganic Chemistry
Immune system
familial adenomatous polyposis
Biomarkers
Tumor
medicine
Humans
Cell Lineage
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Aged
Tumor microenvironment
business.industry
Organic Chemistry
medicine.disease
digestive system diseases
Dysplasia
Cancer research
business
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 18
International Journal of Molecular Sciences, Vol 22, Iss 9791, p 9791 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22189791
Popis: Background. 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). Methods. 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). Results. 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. Conclusions. 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.
Databáze: OpenAIRE
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