CD8+ and FOXP3+ Tumor-Infiltrating T Cells Before and After Chemoradiotherapy for Rectal Cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-02-25

AUTHORS

Eiji Shinto, Kazuo Hase, Yojiro Hashiguchi, Akinori Sekizawa, Hideki Ueno, Atsushi Shikina, Yoshiki Kajiwara, Hirotoshi Kobayashi, Megumi Ishiguro, Junji Yamamoto

ABSTRACT

BackgroundCD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression; however, immunomodulation during CRT for rectal cancer has not been thoroughly assessed. We investigated whether neoadjuvant CRT altered the in situ immune cell population and clinical implications of TIL accumulation before and after CRT.MethodsWe recruited 93 rectal cancer patients who underwent neoadjuvant CRT and radical resection. Pretreatment biopsy and post-CRT resected specimens were immunostained for CD8 and FOXP3, and the densities of stromal (STL) and intraepithelial (IEL) immunopositive TILs were determined separately. In addition, 54 patients with resections but without neoadjuvant CRT were enrolled for comparison.ResultsCD8+ STL density doubled after CRT (average counts: 92 vs. 230 per microscopic field using a 20 × objective lens; P < 0.0001), whereas FOXP3+ STL counts remained stable (109 vs. 109). Compared with non-CRT cases, CRT increased CD8+ STL density. Multivariate analyses demonstrated that high post-CRT CD8 + STL density was associated with better prognosis (5-year recurrence-free survival: 87.5 vs. 57.8 %; P = 0.0058) and that a high pretreatment CD8/FOXP3 IEL ratio was a predictor of favorable tumor regression (P = 0.0029).ConclusionsFavorable anticancer immunity occurred after CRT for rectal cancer by altering TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density after CRT were associated with a favorable clinical outcome. More... »

PAGES

414-421

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-014-3584-y

DOI

http://dx.doi.org/10.1245/s10434-014-3584-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019005605

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24566864


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35 schema:description BackgroundCD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression; however, immunomodulation during CRT for rectal cancer has not been thoroughly assessed. We investigated whether neoadjuvant CRT altered the in situ immune cell population and clinical implications of TIL accumulation before and after CRT.MethodsWe recruited 93 rectal cancer patients who underwent neoadjuvant CRT and radical resection. Pretreatment biopsy and post-CRT resected specimens were immunostained for CD8 and FOXP3, and the densities of stromal (STL) and intraepithelial (IEL) immunopositive TILs were determined separately. In addition, 54 patients with resections but without neoadjuvant CRT were enrolled for comparison.ResultsCD8+ STL density doubled after CRT (average counts: 92 vs. 230 per microscopic field using a 20 × objective lens; P < 0.0001), whereas FOXP3+ STL counts remained stable (109 vs. 109). Compared with non-CRT cases, CRT increased CD8+ STL density. Multivariate analyses demonstrated that high post-CRT CD8 + STL density was associated with better prognosis (5-year recurrence-free survival: 87.5 vs. 57.8 %; P = 0.0058) and that a high pretreatment CD8/FOXP3 IEL ratio was a predictor of favorable tumor regression (P = 0.0029).ConclusionsFavorable anticancer immunity occurred after CRT for rectal cancer by altering TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density after CRT were associated with a favorable clinical outcome.
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42 schema:keywords BackgroundCD8
43 CD8
44 CD8/FOXP3 IEL ratio
45 CD8/FOXP3 TIL ratios
46 CRT CD8
47 ConclusionsFavorable anticancer immunity
48 FOXP3 IEL ratio
49 FOXP3 TIL ratios
50 Foxp3
51 IEL ratio
52 MethodsWe
53 P3
54 ResultsCD8
55 STL counts
56 STL density
57 TIL accumulation
58 TIL ratio
59 TIL subsets
60 accumulation
61 addition
62 analysis
63 anticancer immunity
64 better prognosis
65 biopsy
66 box P3
67 cancer
68 cancer patients
69 cases
70 cell populations
71 cells
72 chemoradiotherapy
73 clinical implications
74 clinical outcomes
75 comparison
76 counts
77 density
78 favorable clinical outcome
79 favorable tumor regression
80 high CD8/FOXP3 IEL ratio
81 high CD8/FOXP3 TIL ratios
82 high pretreatment CD8/FOXP3 IEL ratio
83 higher CD8
84 immune cell populations
85 immunity
86 immunomodulation
87 immunopositive TILs
88 implications
89 improved survival
90 intraepithelial (IEL) immunopositive TILs
91 lymphocytes
92 major players
93 multivariate analysis
94 neoadjuvant chemoradiotherapy
95 non-CRT cases
96 outcomes
97 patients
98 players
99 population
100 predictors
101 pretreatment CD8/FOXP3 IEL ratio
102 pretreatment biopsies
103 prognosis
104 radical resection
105 ratio
106 rectal cancer
107 rectal cancer patients
108 regression
109 resection
110 specimens
111 subset
112 survival
113 tumor immunity
114 tumor regression
115 tumor-infiltrating lymphocytes
116 tumors
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