The clinical significance of tertiary lymphoid structure and its relationship with peripheral blood characteristics in patients with surgically resected non-small cell lung cancer: a single-center, retrospective study

• Published in: Cancer Immunology, Immunotherapy Vol. 71; no. 5; pp. 1129 - 1137
• Main Authors: Fukuhara, Mitsuro, Muto, Satoshi, Inomata, Sho, Yamaguchi, Hikaru, Mine, Hayato, Takagi, Hironori, Ozaki, Yuki, Watanabe, Masayuki, Inoue, Takuya, Yamaura, Takumi, Okabe, Naoyuki, Matsumura, Yuki, Hasegawa, Takeo, Osugi, Jun, Hoshino, Mika, Higuchi, Mitsunori, Shio, Yutaka, Suzuki, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2022; Springer Nature B.V
• Subjects: Antigen-presenting cells; Cancer Research; Carcinoma, Non-Small-Cell Lung - pathology; CD9 antigen; Clinical significance; Cytometry; Histocompatibility antigen HLA; Humans; Immunology; Leukocytes (mononuclear); Leukocytes (neutrophilic); Lung cancer; Lung Neoplasms - pathology; Lymphocytes; Lymphocytes, Tumor-Infiltrating - metabolism; Medical prognosis; Medicine; Medicine & Public Health; Non-small cell lung carcinoma; Oncology; Original; Original Article; Patients; Peripheral blood mononuclear cells; Prognosis; Retrospective Studies; Small cell lung carcinoma; Tertiary Lymphoid Structures - pathology; Tumor Microenvironment; Tumors; Tertiary lymphoid structure; Antigen-presenting cells; Neutrophil to lymphocyte ratio; Non-small cell lung cancer
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-021-03067-3

Introduction The presence of tertiary lymphoid structure (TLS) in tumor tissues has been reported to be a factor associated with a good prognosis in several types of cancers. However, the relationship between TLS formation and peripheral blood findings remains unclear. The purposes of the study were to evaluate the effect of the presence of TLS on survival and determine the peripheral blood characteristics associated with TLS formation in non-small cell lung cancer (NSCLC) patients. Methods A total of 147 consecutive NSCLC patients who underwent lung resection at Fukushima Medical University Hospital between 2013 and 2017 were enrolled. TLS expression was evaluated, and the relationships between clinical parameters and outcomes were analyzed. Peripheral blood mononuclear cells (PBMCs) were further analyzed by mass cytometry to characterize the TLS-positive microenvironment. Results Forty-six patients had high TLS expression, and the remaining 101 patients had low TLS expression. In stage II to IV patients ( n  = 35), disease-free survival was longer in the high TLS expression group ( p  = 0.027). A low neutrophil to lymphocyte ratio (NLR) < 2.75 in the peripheral blood was associated with high TLS expression ( p  = 0.003). Citrus analysis after mass cytometry assay showed that the number of cells expressing HLA-DR and CD9 in PBMCs was lower in the high TLS expression group. Conclusion High TLS expression is associated with a good prognosis after surgery in stage II and III NSCLC patients. In the peripheral blood, a low NLR and few antigen-presenting cells indicate the presence of TLS in the tumor microenvironment.