In situ expression of B7 and CD28 receptor families in human malignant melanoma: Relevance for T‐cell‐mediated anti‐tumor immunity

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Abstract
Work in animal models has suggested that interactions of members of the B7 receptor family (e.g., B7–1, B7–2) on tumor cells with their ligands CD28 and CTLA‐4 on cytotoxic T cells (CTL) are important for the induction of anti‐tumor immunity against malignant melanoma (MM). To determine whether these molecules are of relevance for CTL responses against human MM, we studied the expression of B7–1, B7–2, CD28 and CTLA‐4 in primary tumors of MM (PMM), MM metastases (MMM) and benign melanocytic nevi (BMN) by immunohisto‐chemistry (IH) and by reverse transcription polymerase chain reaction (RT‐PCR). By RT‐PCR, B7–1 and B7–2‐specific mRNAs were detected in most PMM, MMM and BMN. These PCR‐signals were derived from CD45+‐infiltrating leukocytes and not from tumor cells since (1) MMM depleted of CD45+ cells contained no B7–1 or B7–2 mRNA; and (2) by IH, B7–1 and B7–2 were found on infiltrating dendritic cells, macrophages and a variable proportion of tumor‐infiltrating lymphocytes (TIL) but not on melanoma cells or nevus cells. The important exceptions were 5/5 spontaneously regressing PMM, in which B7–1 and B7–2 were expressed by melanoma cells, that were surrounded by TIL expressing CD28 but not CTLA‐4. We conclude that, in PMM, MMM and BMN, the majority of TIL are CD28+ and that B7–1 and B7–2 are expressed by CD45+‐infiltrating antigen‐presenting cells (APC) and TIL, but not by the tumor cells. However, in spontaneously regressing PMM, melanoma cells express B7–1, B7–2 and MHC class‐I and‐II antigens, particularly in areas with clinical and histological signs of an ongoing anti‐tumor response. These data suggest that the absence of B7–1 and B7–2 favors the escape of MM from immunosurveillance, while B7–1, B7–2 expression enhances T‐cell‐mediated anti‐tumor immunity. © 1995 Wiley‐Liss Inc.