Shinkichi Takamori1, Kazuki Takada2, Tetsuzo Tagawa1, Gouji Toyokawa1, Fumihiko Hirai1, Nami Yamashita1, Tatsuro Okamoto1, Eiji Oki1, Tomoharu Yoshizumi1, Yoshinao Oda3, Yoshihiko Maehara1. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka 812-8582, Japan. 2. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan. Electronic address: k_takada@surg2.med.kyushu-u.ac.jp. 3. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi, Fukuoka 812-8582, Japan.
Abstract
BACKGROUND: It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors. METHODS: We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University. The percentages of PD-L1-positive TCs and ICs in lung metastases and the primary tumor were classified into five categories (0: <1%; 1: 1%-4%; 2: 5%-9%; 3: 10%-49%; and 4: ≥50%). Lesions in which ≥1% of the TCs and ICs were PD-L1-positive were considered positive. RESULTS: The primary cancers included rectal (n = 19), colon (n = 10), liver (n = 10), bile duct (n = 2), stomach (n = 1), gall bladder (n = 1) and breast (n = 1). Discrepancies in PD-L1 expression on TCs and ICs between lung metastases and primary lesions were observed in 5 (11.4%, κ = 0.23) and 9 (20.5%, κ = 0.11) of the 44 cases, respectively. PD-L1 expression on ICs was higher in lung metastases than paired primary tumors (p = 0.026), although the percentage of PD-L1-positive TCs was not significantly different between lung metastases and primary tumors (p = 0.767). CONCLUSIONS: There were significant differences in PD-L1 expression on TCs and ICs between lung metastases and primary tumors. Clinicians should be aware of these differences in the tumor microenvironment when treating patients with immunotherapy.
BACKGROUND: It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors. METHODS: We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University. The percentages of PD-L1-positive TCs and ICs in lung metastases and the primary tumor were classified into five categories (0: <1%; 1: 1%-4%; 2: 5%-9%; 3: 10%-49%; and 4: ≥50%). Lesions in which ≥1% of the TCs and ICs were PD-L1-positive were considered positive. RESULTS: The primary cancers included rectal (n = 19), colon (n = 10), liver (n = 10), bile duct (n = 2), stomach (n = 1), gall bladder (n = 1) and breast (n = 1). Discrepancies in PD-L1 expression on TCs and ICs between lung metastases and primary lesions were observed in 5 (11.4%, κ = 0.23) and 9 (20.5%, κ = 0.11) of the 44 cases, respectively. PD-L1 expression on ICs was higher in lung metastases than paired primary tumors (p = 0.026), although the percentage of PD-L1-positive TCs was not significantly different between lung metastases and primary tumors (p = 0.767). CONCLUSIONS: There were significant differences in PD-L1 expression on TCs and ICs between lung metastases and primary tumors. Clinicians should be aware of these differences in the tumor microenvironment when treating patients with immunotherapy.