Objective:To analyze the effect of CD100 to monocyte cytotoxicity in non-small cell lung cancer (NSCLC) patients.Methods:Thirty-five NSCLC patients and thirteen healthy controls were included from Zhengzhou Central Hospital between March 2018 and September 2018. Peripheral blood mononuclear cells (PBMC) and bronchial alveolar lavage fluid (BALF) (both tumor site and non-tumor site) was collected from NSCLC patients, while PBMC was collected from healthy controls. Monocytes were purified from PBMC and BALF. Membrane-bound CD100 (mCD100) and CD72 expression on monocytes was measured by flow cytometry. Monocytes from NSCLC patients were stimulated with recombinant human CD100, anti-CD72, matrix metalloproteinase 14(MMP14), or anti-CD100, and were co-cultured with NCI-H1882 cells for 48 h. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), granzyme A, granzyme B level in the supernatants, CD16 expression on monocytes, and percentage of target cell death was assessed. Student t test or paired t test was used for comparison. Results:There were no significant differences of peripheral CD14 + mCD100 + percentage, CD14 + CD72 + percentage, CD100 mean fluorescence intensity (MFI), CD72 MFI between NSCLC patients and healthy controls ( P>0.05). CD14 + mCD100 + percentage, CD14 + CD72 + percentage, CD100 MFI, CD72 MFI was remarkably elevated in tumor site compared with in non-tumor site in NSCLC patients ( P<0.05). There was no remarkable difference of peripheral monocytes-induced NCI-H1882 cell death between NSCLC group and control group [(13.95±3.16)% vs (13.22±2.40)%, P=0.451]. Lung-resident monocytes-induced NCI-H1882 cell death was reduced in tumor site when compared with non-tumor site [(11.61±2.81)% vs (14.19±3.57)%, P=0.008 7]. TNF-α, IL-1β, granzyme A, granzyme B level was also decreased in the supernatants of monocytes from tumor site compared with non-tumor site in NSCLC patients( P<0.05). However, there was no statistical difference of CD16 level between two groups( P=0.666). Recombinant human CD100 stimulation promoted NCI-H1882 cell death induced by monocytes from tumor site when compared with unstimulated cells ( P<0.000 1). TNF-α, IL-1β, granzyme A, granzyme B level was also increased ( P<0.05). However, Monocytes, which were pretreated with anti-CD72, induced decreased NCI-H1882 cell death and TNF-α, IL-1β, granzyme A, granzyme B secretion in response to recombinant human CD100 stimulation ( P<0.05). Recombinant human MMP14 stimulation decreased CD14 + mCD100 + percentage and increased soluble CD100 (sCD100) level. NCI-H1882 cell death and TNF-α, IL-1β, granzyme A, granzyme B level was elevated when compared with unstimulated cells ( P<0.05). Anti-CD100 administration decreased sCD100 level. NCI-H1882 cell death and TNF-α, IL-1β, granzyme A, granzyme B level was elevated when compared with MMP14 stimulated cells ( P<0.05). Conclusions:CD100 shedding was insufficient in tumor infiltrating monocytes in NSCLC patients, leading to decreased cytotoxicity. MMP14 might elevate cytotoxicity of tumor infiltrating monocytes via promoting CD100 shedding and sCD100 formation.