TY - JOUR
T1 - Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer
AU - Kinoshita, T.
AU - Muramatsu, R.
AU - Fujita, T.
AU - Nagumo, H.
AU - Sakurai, T.
AU - Noji, S.
AU - Takahata, E.
AU - Yaguchi, T.
AU - Tsukamoto, N.
AU - Kudo-Saito, C.
AU - Hayashi, Y.
AU - Kamiyama, I.
AU - Ohtsuka, T.
AU - Asamura, H.
AU - Kawakami, Yutaka
N1 - Funding Information:
This work was supported by the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT), Project for Cancer Research And Therapeutic Evolution (PCREATE) from Japan Agency for Medical Research and Development (AMED), grants-in-aid for Scientific Research (S) (26221005) from Ministry of Education, Culture, Sports, Science and Technology (MEXT), and a grant from Tokyo Biochemical Research Foundation. We are grateful to the Collaborative Research Resources, School of Medicine, Keio University, for technical support and reagents.
Publisher Copyright:
© The Author 2016.
PY - 2016/11
Y1 - 2016/11
N2 - Background: T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. Patients and methods: We evaluated the prognostic significance of TILs (CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. Results: In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05 for recurrencefree survival (RFS)] and a low accumulation of CD20+ B cells (HR: 2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01 for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01 for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells (HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an unfavorable factor in non-smokers with AD. Conclusions: A low number of CD8+ T cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of CD20+ B cells in non-smokers with AD were identified as independent unfavorable prognostic factors in resected NSCLC. Evaluating the influence of histological type and smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC.
AB - Background: T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. Patients and methods: We evaluated the prognostic significance of TILs (CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. Results: In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05 for recurrencefree survival (RFS)] and a low accumulation of CD20+ B cells (HR: 2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01 for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01 for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells (HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an unfavorable factor in non-smokers with AD. Conclusions: A low number of CD8+ T cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of CD20+ B cells in non-smokers with AD were identified as independent unfavorable prognostic factors in resected NSCLC. Evaluating the influence of histological type and smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC.
KW - Histological type
KW - Non-small-cell lung cancer
KW - Prognostic factor
KW - Smoking habit
KW - Tumor-infiltrating lymphocytes
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U2 - 10.1093/annonc/mdw319
DO - 10.1093/annonc/mdw319
M3 - Article
C2 - 27502728
AN - SCOPUS:85019841393
SN - 0923-7534
VL - 27
SP - 2117
EP - 2123
JO - Annals of Oncology
JF - Annals of Oncology
IS - 11
ER -
