Inhibition of Immune Pathway May Trigger Melanoma Growth
Colocalization of immune inhibitory B7-H1 and tumor-infiltrating lymphocytes seen in melanocytes
MONDAY, April 2 (HealthDay News) -- Melanocyte expression of an immune inhibitory molecule, B7-H1, is associated with the presence of tumor-infiltrating lymphocytes (TILs), according to a study published in the March 28 issue of Science Translational Medicine.
In an effort to understand the association between B7-H1 and TILs, Janis M. Taube, M.D., from the Johns Hopkins Medical Institutions in Baltimore, and colleagues examined the expression of B7-H1 in melanocytes and primary and metastatic melanomas.
The researchers found that 98 percent of B7-H1+ tumors, and only 28 percent of B7-H1− tumors, were associated with TILs. The inflammatory cytokine interferon-γ, which induces B7-H1, was found at the interface of B7-H1+ tumors, but not B7-H1− tumors. The investigators theorized that TILs may secrete interferon-γ, triggering their own inhibition. Consistent with this, patients with B7-H1+ metastatic melanoma survived significantly longer than patients with B7-H1− metastatic melanomas.
"Induction of the B7-H1/PD-1 pathway may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity and may explain how melanomas escape immune destruction despite endogenous antitumor immune responses," Taube and colleagues conclude. "These observations suggest that therapies that block this pathway may benefit patients with B7-H1+ tumors."
Several authors disclosed receiving research support from Bristol-Myers Squibb.