Impaired th1/tc1 cytokine production of tumor-infiltrating lymphocytes in a model of primary intraocular B-cell lymphoma.
OBJECTIVE
Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma with a pathogenesis that is still unclear. Microenvironment is known to be crucial in controlling tumor growth and maintenance. To study the immune microenvironment in intraocular lymphomas and to characterize the cytokine polarization of infiltrating T-lymphocytes, a new murine model of intraocular B-cell lymphoma was developed.


METHODS
Immunocompetent adult mice were injected intravitreally with a syngeneic lymphomatous B-cell line. Clinical, histologic, and flow cytometric analyses were performed to characterize the tumoral invasion and the immune infiltration. Cytokine production of ocular cells was investigated by RT-PCR and fluorescent immunoassay, with or without stimulation by anti-CD3(+) anti-CD28 antibodies.


RESULTS
Intraocular lymphoma developed in eyes injected by lymphomatous B-cells. At day 19, the retina and the vitreous cavity were infiltrated by tumor cells. Up to 15% of living cells were T-lymphocytes. Cytokine profile analysis of the supernatant of ocular cells cultured ex vivo demonstrated the presence of IL10, IL6, IFNgamma, and TNFalpha. Stimulation of ocular cells with anti-CD3(+) anti-CD28 antibodies increased the IFNgamma level and led to the induction of IL2 production, completing the type 1 (Th1/Tc1-like) pattern of cytokine expression observed. IL12p70 and IL4, potent Th1 or Th2 differentiating factors, were undetectable, even after stimulation.


CONCLUSIONS
The results suggest that T-cells from intraocular B-lymphomas are characterized by a Th1/Tc1-like profile that could be partially inhibited in vivo. These data raise the possibility of a T-cell immunostimulation to reactivate the Th1/Tc1-lymphocytes and improve intraocular antitumoral immunity.
Touitou
Valérie
V
Immune Microenvironment and Tumors Group, INSERM UMRS872, Université Pierre et Marie Curie-Paris, France.
Daussy
Cécile
C
Bodaghi
Bahram
B
Camelo
Serge
S
de Kozak
Yvonne
Y
Lehoang
Phuc
P
Naud
Marie-Christine
MC
Varin
Audrey
A
Thillaye-Goldenberg
Brigitte
B
Merle-Béral
Hélène
H
Fridman
Wolf Herman
WH
Sautès-Fridman
Catherine
C
Fisson
Sylvain
S
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection; D014822:Vitreous Body / Q000473:pathology*
D016207:Cytokines