We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and beta 2-microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell.

No abstract

We attempted to generate continuous in vitro cultures from patients with mycosis fungoides and the Sezary syndrome (cutaneous T-cell lymphomas, CTCL). Using conventional culture techniques without mitogen stimulation. multiple attempts (32 specimens from 25 patients) failed to replicate T cells. but 6 B-lymphoblastoid cultures were established. Athymic nude mice injected by a variety of routes with CTCL cells from 1 3 patients failed to develop tumors; however. the B-lymphoblastoid cultures were tumorigenic. Lymphocytes from 6 healthy donors and CTCL cells from 7 patients were seeded in growth medium supplemented with one of the following mitogens: phytohemagglutinin (PHA). concanavalin A (Con-A). lymphocyte-conditioned medium (LyCM). pokeweed mitogen (PWM), and staphylococcal protein-A. Normal lymphocytes failed to replicate for more than a few days except in LyCM, where viability and replication remained absolutely dependent on the continued presence of the mitogen. In contrast, mitogen-induced proliferation of CTCL cells was variable, and 1 or more of 4 mitogens induced replication in 4 CTCL cultures. There was partial correlation between the ability of mitogens to stimulate CTCL cells in lymphocyte transformation assays and their ability to act as growth factors. CTCL cells were more resistant to the toxic effects of mitogens than lymphocytes from normal donors, permitting the use of mitogens as long-term growth factors. Two long-term CTCL cultures were established. one after stimulation with Con-A, and the other with LyCM. The cultures required mitogens only for initial growth and have proliferated without mitogens for over a year. The cultures retained many of the features of the CTCL cells present in the patients from whom they were derived, but differed from each other in morphology, E-rosette formation. DNA content, and tumorigenicity. Cytochemical studies provided further evidence of their T-ceIl origin. Both cultures released macrophage inhibitory factor.

into DNA that expressed c-myc mRNA. In addition, one clone with an integrated neo gene but a deleted c-myc gene was isolated and in this case c-myc was not expressed. C-myc expression in transfected clones was associated with altered large cell morphology, a shorter doubling time, and increased cloning efficiency, but no difference in L dopa decarboxylase levels and bombesinlike immunoreactivity. We conclude increased c-myc expression observed here in transfected clones correlates with some of the phenotypic properties distinguishing c-myc amplified variants from unamplified classic small cell lung cancer lines.

No abstract