ASPO Abstracts
T cell landscapes of colorectal adenomas
Category: Molecular Epidemiology & Environment
Conference Year: 2020
Abstract Body:
Purpose of the study: Lymphocytic infiltration is a positive prognostic indicator for
colorectal cancer outcomes, but the immune landscapes of precancerous lesions have
not been thoroughly explored. In this study, we characterized the T cell receptor
repertoires of colorectal adenomas and compared quantity and clonality features of
tumor-associated T cells across adenoma subtypes.
Methods: Thirteen fresh frozen and 17 formalin-fixed paraffin-embedded (FFPE)
adenoma samples were collected from 22 Moffitt Cancer Center Total Cancer Care
participants, including 8 synchronous lesions from 4 patients. Adenomas were classified
into low- and high-risk categories based on American Gastroenterological Association
guidelines. T cell receptor complementarity-determining region 3 (CDR3) sequences
were determined using the DNA-based immunoSEQ assay (Adaptive Biotechnologies).
Relative T cell abundance and clonality were compared across adenomas subtypes
using linear regression models adjusted for tissue type, age, and sex. The overlap of
CDR3 amino acid sequences across synchronous lesions was also examined to identify
common receptors potentially recognizing specific predicted neoantigens. Multiplex
immunofluorescence (Vectra 3.0, Perkin Elmer) was conducted on the FFPE adenoma
tissues to measure density and location of specific T cell subtypes.
Results: High-risk adenomas had significantly lower T cell infiltration compared to low-
risk adenomas (RR=0.26, 95%CI=0.13-0.51, P<0.001). High-risk adenomas also had
significantly higher clonality values, indicative of a less diverse T cell response (RR=1.74,
95%CI=1.20-2.53, P<0.01). Synchronous lesions had similar T cell repertoires, as
demonstrated by the partial overlap in CDR3 amino acid sequences, but no putative
tumor neoantigens were identified.
Conclusions: To our knowledge, this is the first study to investigate the T cell receptor
repertoires of colorectal adenomas. Our findings suggest that low T cell quantity and
diversity in the adenoma microenvironment are associated with high-risk
histopathological features and that immune-related biomarkers could be used to identify
patients who may benefit from more frequent surveillance or novel immunoprevention
strategies.
Keywords: colorectal adenoma, immune response, prevention