Systemic inflammation is associated with the density of immune cells in the tumor microenvironment of gastric cancer.
BACKGROUND
The neutrophil-lymphocyte ratio (NLR) and the prognostic nutritional index (PNI) are markers of systemic inflammation known to be useful prognostic indicators of malignancy. However, little evidence has defined the influence of inflammation on the tumor microenvironment.


METHODS
Two hundred eighty-eight patients who underwent curative surgery for gastric cancer were included. Preoperative peripheral blood samples were used to analyze the NLR and PNI. The optimal cutoff levels for the NLR and PNI were defined by receiver operating characteristic curve analysis for survival (NLR = 2.7, PNI = 47.7). The densities of specific immune cells (CD3+, CD4+, CD8+) within the tumor microenvironment were measured in tumor microarrays by immunohistochemical analysis.


RESULTS
Two hundred thirty-five patients (81.6 %) had a low NLR and 53 patients (18.4 %) had a high NLR. One hundred seventeen patients (40.6 %) had a low PNI and 171 patients (59.4 %) had a high PNI. CD3+and CD8+immune cell density were not associated with the NLR and PNI. However, in the high-NLR group compared with the low-NLR group, CD4+immune cell density was significantly decreased (P < 0.001). Similarly, the density of CD4+immune cells was also significantly decreased in the low-PNI group compared with the high-PNI group (P = 0.007). A high NLR and a low PNI were correlated with worse overall survival in multivariate analysis (P = 0.028 and P = 0.002 respectively).


CONCLUSIONS
The NLR and PNI are associated with the density of CD4+immune cells in the tumor microenvironment, which leads to prognostic values of systemic inflammation in gastric cancer.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Yeonjoo
Y
Choi
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea. jwkim@snubh.org.
Jin Won
http://orcid.org/0000-0002-1357-7015
JW
Kim
Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, 875, Haeun-daero, Haeundae-gu, Busan, 48108, Republic of Korea.
Kyung Han
KH
Nam
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Song-Hee
SH
Han
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Ji-Won
JW
Kim
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Sang-Hoon
SH
Ahn
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Do Joong
DJ
Park
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Keun-Wook
KW
Lee
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Hye Seung
HS
Lee
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.
Hyung-Ho
HH
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D015596:Nutrition Assessment; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*
Gastric cancer; Immune cell; Neutrophil–lymphocyte ratio; Prognostic nutritional index; Tumor microenvironment
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