Survival in rectal cancer is predicted by T cell infiltration of tumour-associated lymphoid nodules

Lymphoid nodules are a normal component of the mucosa of the rectum, but little is known about their function and whether they contribute to the host immune response in malignancy. In rectal cancer specimens from patients with local (n = 18), regional (n = 12) and distant (n = 10) disease, we quanti...

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Published in:	Clinical and experimental immunology Vol. 161; no. 1; pp. 81 - 88
Main Authors:	McMullen, T.P.W, Lai, R, Dabbagh, L, Wallace, T.M, de Gara, C.J
Format:	Journal Article
Language:	English
Published:	Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-07-2010 Blackwell Publishing Ltd Blackwell Oxford University Press Blackwell Science Inc
Subjects:	Adenocarcinoma - immunology Adenocarcinoma - mortality Adenocarcinoma - pathology Adenocarcinoma - secondary Aged Analytical, structural and metabolic biochemistry Antigens, CD - analysis Antigens, CD1 - analysis Biological and medical sciences CD3 Complex - analysis CD83 Antigen colorectal neoplasms dendritic cell Dendritic Cells - chemistry Dendritic Cells - immunology Dendritic Cells - pathology Female Follow-Up Studies Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Humans Immunoglobulins - analysis Immunophenotyping Interleukin-2 Receptor alpha Subunit - analysis Intestinal Mucosa - immunology Intestinal Mucosa - pathology Kaplan-Meier Estimate Lymphocytes, Tumor-Infiltrating - chemistry Lymphocytes, Tumor-Infiltrating - immunology lymphoid nodule Lymphoid Tissue - pathology Male Medical sciences Membrane Glycoproteins - analysis Middle Aged Neoplasm Invasiveness - immunology Prognosis rectal cancer Rectal Neoplasms - immunology Rectal Neoplasms - mortality Rectal Neoplasms - pathology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus T cell T-Lymphocyte Subsets - chemistry T-Lymphocyte Subsets - immunology Translational Studies Tumors Dendritic cell Rectal disease T cell Prediction rectal cancer Biochemistry Malignant tumor Rectum cancer Survival Nodule lymphoid nodule Antigen presenting cell T-Lymphocyte Digestive diseases Intestinal disease Infiltration Predictive factor Anorectal disease Tumor cell Cancer
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Summary:	Lymphoid nodules are a normal component of the mucosa of the rectum, but little is known about their function and whether they contribute to the host immune response in malignancy. In rectal cancer specimens from patients with local (n = 18), regional (n = 12) and distant (n = 10) disease, we quantified T cell (CD3, CD25) and dendritic cell (CD1a, CD83) levels at the tumour margin as well as within tumour-associated lymphoid nodules. In normal tissue CD3⁺, but not CD25⁺, T cells are concentrated at high levels within lymphoid nodules, with significantly fewer cells found in surrounding normal mucosa (P = 0·001). Mature (CD83), but not immature (CD1a), dendritic cells in normal tissue are also found clustered almost exclusively within lymphoid nodules (P = < 0·0001). In rectal tumours, both CD3⁺ T cells (P = 0·004) and CD83⁺ dendritic cells (P = 0·0001) are also localized preferentially within tumour-associated lymphoid nodules. However, when comparing tumour specimens to normal rectal tissue, the average density of CD3⁺ T cells (P = 0·0005) and CD83⁺ dendritic cells (P = 0·0006) in tumour-associated lymphoid nodules was significantly less than that seen in lymphoid nodules in normal mucosa. Interestingly, regardless of where quantified, T cell and dendritic cell levels did not depend upon the stage of disease. Increased CD3⁺ T cell infiltration of tumour-associated lymphoid nodules predicted improved survival, independent of stage (P = 0·05). Other T cell (CD25) markers and different levels of CD1a⁺ or CD83⁺ dendritic cells did not predict survival. Tumour-associated lymphoid nodules, enriched in dendritic cells and T cells, may be an important site for antigen presentation and increased T cell infiltration may be a marker for improved survival.
Bibliography:	http://dx.doi.org/10.1111/j.1365-2249.2010.04147.x ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-9104 1365-2249
DOI:	10.1111/j.1365-2249.2010.04147.x