Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer.
BACKGROUND
The purpose of this study was to investigate whether tumor-infiltrating immune cells in biopsy specimens can be used to predict the clinical outcome of stage IV nonsmall cell lung cancer (NSCLC) patients.


METHODS
The authors performed an immunohistochemical study to identify and count the number of CD68(+) macrophages, c-kit(+) mast cells, and CD8(+) T cells in both cancer nests and cancer stroma in pretreatment biopsy specimens obtained from 199 patients with stage IV NSCLC treated by chemotherapy, and then analyzed for correlations between the number of immune cells and clinical outcome, including chemotherapy response and prognosis.


RESULTS
There was no correlation between the number of immune cells in either cancer nests or stroma and chemotherapy response. Patients with more tumor-infiltrating macrophages in cancer nests than in cancer stroma (macrophages, nests > stroma) had significantly better survival than nests < stroma cases median survival time (MST 440 days vs 199 days; P < .0001). Patients with more tumor-infiltrating CD8(+) T cells in cancer nests than in cancer stroma (CD8(+) T cells: nests > stroma) showed significantly better survival than in nests < stroma cases (MST 388 days vs 256 days; P = .0070). The proportion of tumor-infiltrating macrophages or CD8(+) T cells between cancer nests and stroma became independent prognostic factors in the multivariate analysis. Neither the number of mast cells in nests nor in stroma correlated with the clinical outcome.


CONCLUSIONS
Evaluation of the numbers of macrophages and CD8(+) T cells in cancer nests and stroma are useful biomarkers for predicting the prognosis of stage IV NSCLC patients treated with chemotherapy, but could fail to predict chemotherapy response.
Kawai
Osamu
O
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Ishii
Genichiro
G
Kubota
Kaoru
K
Murata
Yukinori
Y
Naito
Yoichi
Y
Mizuno
Tetsuya
T
Aokage
Keiju
K
Saijo
Nagahiro
N
Nishiwaki
Yutaka
Y
Gemma
Akihiko
A
Kudoh
Syoji
S
Ochiai
Atsushi
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule