Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.

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. 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. 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 recurrence-free 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. 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.

Kinoshita T ，Muramatsu R ，Fujita T ，Nagumo H ，Sakurai T ，Noji S ，Takahata E ，Yaguchi T ，Tsukamoto N ，Kudo-Saito C ，Hayashi Y ，Kamiyama I ，Ohtsuka T ，Asamura H ，Kawakami Y ... -  《-》

Prognostic Relevance of the Relative Presence of CD4, CD8 and CD20 Expressing Tumor Infiltrating Lymphocytes in Operable Non-small Cell Lung Cancer Patients.

Non-small cell lung cancer (NSCLC) is one of the most lethal tumors. Given the failure of conventional therapeutic strategies, immunotherapy has emerged as a promising treatment modality that may improve the survival of patients with operable and advanced disease. We examined the relative presence of CD20+ B-cells, CD8+ cytotoxic, and CD4+ helper/regulatory T-cells in the tumor-infiltrating lymphocyte (TIL)-population in a series of surgically-treated NSCLCs, and assessed their role as prognostic indicators after surgery. A high percent of CD4+ and CD8+ TILs in the tumor stroma was linked with poor (p=0.003) and good prognosis (p=0.01), respectively. High CD4/CD8 ratio defined a significantly worst prognosis [median survival 22 months vs. undefined, p=0.0002, hazard ratio (HR) 0.3 vs. 3.0]. Statistically significant results were also noted when the analysis was focused on the invading tumor front. In a multivariate model, the CD4/CD8-ratio assessed in the tumor stroma and the stage of disease were independent prognostic variables (p=0.0001, HR=4.1 and p=0.001, HR=1.5, respectively). The balance between CD4+ and CD8+ lymphocytes infiltrating the tumor stroma is a crucial factor defining anti-tumor immune surveillance, has strong prognostic value, and may be tested as a predictive biomarker for immunotherapy in operable NSCLC.

Giatromanolaki A ，Anestopoulos I ，Panayiotidis MI ，Mitrakas A ，Pappa A ，Koukourakis MI ... -  《-》

Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma.

Kinoshita T ，Kudo-Saito C ，Muramatsu R ，Fujita T ，Saito M ，Nagumo H ，Sakurai T ，Noji S ，Takahata E ，Yaguchi T ，Tsukamoto N ，Hayashi Y ，Kaseda K ，Kamiyama I ，Ohtsuka T ，Tomizawa K ，Shimoji M ，Mitsudomi T ，Asamura H ，Kawakami Y ... -  《-》

Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer.

Al-Shibli KI ，Donnem T ，Al-Saad S ，Persson M ，Bremnes RM ，Busund LT ... -  《CLINICAL CANCER RESEARCH》

Combined Evaluation of Tumor-Infiltrating CD8 + and FoxP3 + Lymphocytes Provides Accurate Prognosis in Stage IA Lung Adenocarcinoma.

Kinoshita F ，Takada K ，Yamada Y ，Oku Y ，Kosai K ，Ono Y ，Tanaka K ，Wakasu S ，Oba T ，Osoegawa A ，Tagawa T ，Shimokawa M ，Oda Y ，Mori M ... -  《-》