Effect of neoadjuvant chemoradiation on tumor-infiltrating/associated lymphocytes in locally advanced rectal cancers

Stephanie H Lim; Wei Chua; Christina Cheng; Joseph Descallar; Weng Ng; Michael Solomon; Les Bokey; Karen Wong; Mark T Lee; Paul de  Souza; Joo-Shik Shin; Cheok Soon Lee

Effect of neoadjuvant chemoradiation on tumor-infiltrating/associated lymphocytes in locally advanced rectal cancers

Anticancer Res. 2014 Nov;34(11):6505-13.

Authors

Stephanie H Lim¹, Wei Chua², Christina Cheng³, Joseph Descallar⁴, Weng Ng², Michael Solomon⁵, Les Bokey⁶, Karen Wong⁷, Mark T Lee⁸, Paul de Souza⁹, Joo-Shik Shin¹⁰, Cheok Soon Lee¹¹

Affiliations

¹ Department of Medical Oncology, Liverpool Hospital, Liverpool, Australia Ingham Institute for Applied Medical Research, Liverpool, Australia University of New South Wales, Kensington, Australia stephanie.lim@sswahs.nsw.gov.au.
² Department of Medical Oncology, Liverpool Hospital, Liverpool, Australia Ingham Institute for Applied Medical Research, Liverpool, Australia.
³ Molecular Medicine Research Group, University of Western Sydney, Liverpool, Australia.
⁴ Ingham Institute for Applied Medical Research, Liverpool, Australia University of New South Wales, Kensington, Australia.
⁵ Department of Colorectal Surgery, Royal Prince Alfred Hospital, Camperdown, Australia University of Sydney, Camperdown, Australia Surgical Outcomes Research Centre, Sydney, Australia.
⁶ Ingham Institute for Applied Medical Research, Liverpool, Australia University of Western Sydney, Campbelltown, Australia Department of Colorectal Surgery, Liverpool Hospital, Liverpool, Australia.
⁷ Ingham Institute for Applied Medical Research, Liverpool, Australia University of New South Wales, Kensington, Australia Department of Radiation Oncology, Liverpool Hospital, Liverpool, Australia.
⁸ University of New South Wales, Kensington, Australia Department of Radiation Oncology, Liverpool Hospital, Liverpool, Australia.
⁹ Department of Medical Oncology, Liverpool Hospital, Liverpool, Australia Ingham Institute for Applied Medical Research, Liverpool, Australia University of New South Wales, Kensington, Australia Molecular Medicine Research Group, University of Western Sydney, Liverpool, Australia University of Western Sydney, Campbelltown, Australia.
¹⁰ Ingham Institute for Applied Medical Research, Liverpool, Australia Molecular Medicine Research Group, University of Western Sydney, Liverpool, Australia University of Western Sydney, Campbelltown, Australia Department of Anatomical Pathology, Liverpool Hospital, Liverpool, Australia.
¹¹ Ingham Institute for Applied Medical Research, Liverpool, Australia University of New South Wales, Kensington, Australia Molecular Medicine Research Group, University of Western Sydney, Liverpool, Australia University of Sydney, Camperdown, Australia University of Western Sydney, Campbelltown, Australia Department of Anatomical Pathology, Liverpool Hospital, Liverpool, Australia.

PMID: 25368252

Abstract

Background: Lymphocytes and natural killer cells (NK) appear to be important in colorectal cancer. Their role in chemoradiotherapy for rectal cancers is unclear. We evaluated T-lymphocytes (CD3), sub-groups CD4 and CD8, and NK cells (CD56+CD57) in normal and rectal tumor tissues pre- and post-chemoradiotherapy, and investigated their relationship to tumor regression grade, disease-free survival and pathological stage.

Materials and methods: Tissue microarrays from colonoscopic biopsies, resection specimens and normal tissues, from 52 patients, were immunostained.

Results: NK cell counts were significantly lower in tumor samples compared to normal tissues (p=0.007). T-lymphocyte counts were higher in post-treatment compared to pre-treatment samples (p=0.025), specifically in the CD8 subgroup after long-course treatment. The results suggested an association between post-treatment CD8 and NK cell counts with higher tumor regression. No associations were found with regard to stage or disease-free survival.

Conclusion: NK cell counts were significantly reduced in rectal cancers compared to normal tissues, while total T-lymphocyte counts increased post-chemoradiotherapy. Both appeared important in tumor regression.

Keywords: CD3/CD4/CD8 lymphocytes; NK cells; colorectal cancer; radiation; tumour microenvironment.

Publication types

Comparative Study
Randomized Controlled Trial

MeSH terms

Antimetabolites, Antineoplastic / therapeutic use
Case-Control Studies
Chemoradiotherapy*
Female
Fluorouracil / therapeutic use*
Follow-Up Studies
Humans
Killer Cells, Natural / drug effects
Killer Cells, Natural / radiation effects
Lymphocytes, Tumor-Infiltrating / drug effects*
Lymphocytes, Tumor-Infiltrating / radiation effects*
Male
Middle Aged
Neoadjuvant Therapy*
Neoplasm Staging
Prognosis
Rectal Neoplasms / mortality
Rectal Neoplasms / pathology
Rectal Neoplasms / therapy*
Retrospective Studies
Survival Rate
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / radiation effects
Tissue Array Analysis

Substances

Antimetabolites, Antineoplastic
Fluorouracil