Role of tumor-associated macrophages (TAM) in advanced gastric carcinoma: the impact on FasL-mediated counterattack.
BACKGROUND
Exactly what role does tumor-derived Fas ligand (FasL) play in cancer: maintaining the immune privilege site or inducing a pro-inflammatory effect? One possible hypothesis is that tumor-associated macrophages (TAM) act as the mediator that enables apoptosis of anti-tumor immune cells without FasL-related inflammation. We have evaluated the tumor FasL expression and TAM along the tumor margin and/or in cancer stroma, and their impact on the infiltration of immune-competent cells into the tumor nest.


METHODS
Tissue specimens from consecutive 84 advanced gastric carcinoma patients, who had undergone a curative resection, were evaluated for TAM (CD68+ cells), tumor FasL expression and immune status (CD8 + T cells).


RESULTS
A high number of TAM significantly correlated with lymph node metastasis, intestinal type tumor and FasL expression. Although TAM had a tendency for an inverse correlation with the number of CD8+ T cells within the tumor nest (nest CD8) (p=0.0592), there was no correlation between FasL expression and nest CD8 (p=0.2158). This inverse association was found to be stronger in cases with both FasL-positive and high TAM tumors than in others (p=0.0139). The combination parameter of FasL-positive and high TAM became an independent prognostic factor in Cox's multivariate analysis, along with the pT status, nest CD8 and tumor cell apoptosis.


CONCLUSIONS
We suggest that TAM works harmoniously with tumor-derived FasL and serves as a barrier against the infiltration of CD8+ T cells into the cancer nest.
Ohno
Satoshi
S
Department of Complementary and Alternative Medicine, Kanazawa University, Graduate School of Medical Science, Ishikawa, Japan. satoshio@med.kanazawa-u.ac.jp
Inagawa
Hiroyuki
H
Dhar
Dipok Kumar
DK
Fujii
Toshiyuki
T
Ueda
Shuhei
S
Tachibana
Mitsuo
M
Ohno
Yumiko
Y
Suzuki
Nobutaka
N
Inoue
Masaki
M
Soma
Gen-Ichiro
G
Nagasue
Naofumi
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D017209:Apoptosis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008833:Microcirculation; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012008:Recurrence; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D016827:CD8 Antigens; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C505661:FASLG protein, human