Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response.
A poorly immunogenic murine colon cancer was used to investigate mechanisms of antitumor immunity. Injection of tumor cells engineered by gene transfection to secrete IL-2 stimulated an MHC class I-restricted cytolytic T lymphocyte (CTL) response against the parental tumor. The tumor cells secreting IL-2 produced an antitumor response in vivo, even in the absence of CD4+ T cells. Animals immunized with the engineered cells were protected against subsequent challenge with the parental tumor cell line. Similar findings were demonstrated for other tumor types. Thus, provision of a helper lymphokine in a paracrine fashion induced a tumor-specific immune response involving activation of endogenous CTLs and other immune effector cells. These findings demonstrate that the failure of an effective antitumor immune response may be primarily due to a helper arm deficiency of the immune system rather than a paucity of tumor-specific cytotoxic effector cells. Furthermore, they outline a novel strategy for augmenting tumor immunity.
Fearon
E R
ER
Department of Oncology School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205.
Pardoll
D M
DM
Itaya
T
T
Golumbek
P
P
Levitsky
H I
HI
Simons
J W
JW
Karasuyama
H
H
Vogelstein
B
B
Frost
P
P
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015704:CD4 Antigens; D007376:Interleukin-2