Preclinical studies have suggested that cytotoxic agents and radiation may partly
deliver their antitumor activities by activating antitumor immune response. However,
the alterations of tumor immune microenvironment including immunosuppressive molecules
during chemoradiotherapy and their associations with clinical features and prognosis
in rectal cancer have not been thoroughly investigated. Therefore, we investigate
the densities of cluster of differentiation 8 (CD8) positive tumor-infiltrating lymphocytes
(TILs), CD4+TILs, natural killer cell (NK)-TILs, myeloid-derived suppressor cells
(MDSCs), transcription factor forkhead box P3 (FOXP3)+TILs, programmed death ligand-1
(PD-L1), and cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) before and after
neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients to determine their
predictive and prognostic effects. We screen 62 rectal cancer patients who underwent
nCRT followed by radical surgery. Pretreatment biopsy specimens and posttreatment
surgically resected specimens of all patients are retrieved to perform the immunohistochemistry
of CD8, CD4, CD56, FOXP3, CD33, CD11b, PD-L1, and CTLA-4. The CD8+TILs and CD4+TILs
in post-nCRT resected specimens are significantly higher than that in pre-nCRT biopsy
specimens (P = 0.004 and 0.005, respectively). Expressions of MDSC, FOXP3+TILs, and CTLA-4 are
relative stable after nCRT. Tumors with high density of CD8+TILs, CD4+TILs, and low
MDSC-TILs are more sensitive to nCRT (P = 0.022, 0.022 and 0.005, respectively). High pretreatment CD8+TILs are associated
with better disease-free survival and overall survival (P = 0.016 and 0.022, respectively). NK-TILs are detected only in 6 of 62 rectal cancer
specimens evaluated. Cell surface PD-L1 positive by tumor cells (1 of 62) and stroma
cells (3 of 62) are very low. We may conclude that tumor immunity is activated after
nCRT by increased infiltrating CD8+ and CD4+ T cells and relative stable numbers MDSC-TILs,
FOXP3+TILs, and coinhibitory molecules. Pre-nCRT CD8+TILs, CD4+TILs, and MDSC-TILs
are sensitive predictive marker for response to CRT, and high CD8+TILs are associated
with better prognosis.
Abbreviations:
CD8 (cluster of differentiation 8), NK (natural killer cell), MDSCs (myeloid-derived suppressor cells), TILs (tumor-infiltrating lymphocytes), FOXP3 (transcription factor forkhead box P3), PD-L1 (programmed death ligand-1), CTLA-4 (cytotoxic T lymphocyte-associated antigen-4), nCRT (neoadjuvant chemoradiotherapy), LARC (locally advanced rectal cancer), TRG (tumor regression grade), HPF (high-power fields), DFS (disease-free survival), OS (overall survival), CRC (colorectal cancer), DAPI (4′,6-diamidino-2-phenylindole), PD-1 (programmed death 1), IHC (immunohistochemistry), LN (lymph node), HR (hazard ratio)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: July 06, 2015
Accepted:
June 30,
2015
Received in revised form:
June 30,
2015
Received:
February 25,
2015
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
