Immunopathology of metastases in patients of colorectal carcinoma treated with monoclonal antibody 17-1A and granulocyte macrophage colony-stimulating factor.
Twenty patients with metastatic colorectal carcinoma were treated with a single infusion (400 mg) of a mouse monoclonal antibody (IgG2a) against the tumor-associated antigen CO 17-1A and with a daily injection of granulocyte macrophage colony-stimulating factor (GM-CSF) for 10 days. The cycle was repeated every month. Metastases from 5 of the 20 patients biopsied on days 1 and 10 of the first two treatment cycles were studied by immunohistochemistry. During treatment, neutrophils, monocytes, and T lymphocytes increased concordantly in the tumor as in the blood of the individual patient. Macrophages (CD68) and CD8+ T cells infiltrated the tumor glands and displayed TIA-1-reactive cytotoxic granules. Neutrophils were seen mainly in areas of necrosis. Activated (HLA-DR+) CD4+ T cells were usually abundant in the stroma. During treatment, few natural killer cells were found in the tumor, contrary to the marked increase seen in blood. Our observations indicate that GM-CSF markedly recruited activated, tumor-infiltrating leukocytes, possibly representing antibody-dependent cellular cytotoxicity and cytotoxic T effector cells. The notion that combined antibody and GM-CSF therapy may also promote a T-cell antitumor response is further supported and advocated by our findings. The study lends further support to combining GM-CSF with monoclonal antibody-based therapy.
Department of Oncology/Pathology, Karolinska Hospital, Stockholm, Sweden.
J
J
Shetye
P
P
Ragnhammar
M
M
Liljefors
B
B
Christensson
J E
JE
Frödin
P
P
Biberfeld
H
H
Mellstedt
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D003165:Complement System Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D007958:Leukocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003165:Complement System Proteins