[Show abstract][Hide abstract] ABSTRACT: Direct antigen presentation of tumor-associated antigens by tumor cells to T lymphocytes may induce clonal anergy as a mechanism of escape from immune surveillance. B7-1 is a costimulatory molecule for the activation of both CD4+ and CD8+ T lymphocytes that prevents the induction of clonal anergy. Thus, the transfer of B7-1 genes into tumor cells can induce protective immunity and lead to tumor rejection of some tumors in model systems of in vivo tumor growth; however, there is no information on whether stable expression of B7-1 can affect the in vivo growth of squamous cell carcinoma, a common skin cancer. Here, we study how the stable cell surface expression of high levels of B7-1 by Pam 212, a murine squamous cell carcinoma, affects tumor cell-lymphocyte interactions (lymphocyte proliferation and cytotoxicity). Consistent with its costimulatory role, we demonstrate that B7-1 can efficiently induce dendritic epidermal T-cell proliferation in three different dendritic epidermal T-cell cell lines. In addition, B7-1 enhances dendritic epidermal T-cell cytolytic activity against Pam 212 cells in an in vitro 51Cr-release assay, which was blocked by CTLA-4/Ig fusion protein. In contrast to dendritic epidermal T cells, the expression of B7-1 does not alter Pam 212 interactions with either cytotoxic T-lymphocytes, natural killer, or lymphokine-activated killer cells. B7-1 expression by Pam 212 cells did not alter its ability to grow tumors in vivo, as their rate of tumor growth was the same as vector-transfected Pam 212 cells, which were B7-1 negative. Our studies indicate that B7-1 gene transfer into Pam 212 does not alter its tumorigenicity, because it does not alter tumor cell-lymphocyte interactions with cytotoxic T lymphocytes, natural killer cells, and lymphokine-activated killer cells. Further studies of B7-1 modified Pam 212 and dendritic epidermal T cells will clarify whether T-cell receptor-gamma/delta-bearing T lymphocytes can play a role in immunotherapy of Pam 212 squamous cell carcinoma.
Journal of Investigative Dermatology 01/1998; 109(6):728-33. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since Pam 212 cells express low levels of class I major histocompatibility (MHC) antigens, we tested their ability to present alloantigens or minor histocompatibility (mH)/minor lymphocyte stimulatory (mls) antigens in disparate hosts. After subcutaneous injection, Pam 212 cells grew progressive tumors in normal BALB/c mice but were rejected rapidly by naive C3H mice (3 weeks) and slowly by DBA/2 mice (8 weeks). Pam 212 cells (high or low class I MHC expression) induced a strong primary MLR in DBA/2 T cells, but a weak BALB/c T-cell response. In contrast, splenic APC (BALB/c) did not induce an MLR, suggesting that Pam 212 cells represented mH antigens to naive DBA/2 T cells. This MLR was blocked by anti-TCR alpha/beta, anti-class II, and anti-CD4 monoclonal antibodies, but was independent of ICAM-1 and B7. Repeated immunization using IFN-gamma-treated Pam 212 cells induced anti-Pam 212 CTL in DBA/2 mice but not in BALB/c mice. DBA/2 T-cell responses did not appear to be mls (MMTV superantigen)-specific, because Pam 212 cells did not express MMTV mRNA detectable by RT-PCR. Pam 212 cells presented non-lymphoid-associated mH antigens that served as potent stimuli for tumor rejection in mH/mls-disparate hosts, which is similar to tumor rejection mediated by MHC alloantigens.
[Show abstract][Hide abstract] ABSTRACT: After intraperitoneal (IP) injection of delta-aminolevulinic acid (ALA), the endogenous porphyrins in murine skin and tumor tissues were determined by a method involving solvent and acid extractions. The results showed that the total amount of porphyrins in the tumor tissues after ALA injection was much higher than that in the skin from the same mice, although the amount of porphyrins in the skin from the ALA-injected mice was higher than that from the saline-injected (control) mice. The porphyrins in the tumor were mostly protoporphyrin and coproporphyrin, with only a small amount of uroporphyrin. The optimum period for porphyrin accumulation in the tumor as well as in the skin was 1 hour after the injection of ALA. As the period was extended to 3 and 6 hours, the amount of porphyrins in these tissues decreased considerably. These findings could be valuable for further application of ALA in the photodynamic therapy of skin cancer.
Chinese medical journal 05/1995; 108(4):286-90. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because keratinocytes are tolerogenic antigen-presenting cells (APC), we investigated the role of B7/BB-1 in reconstituting defective accessory cell (AC) and APC functions by such nonlymphoid cells. KC were induced to stably express B7/BB-1 by DNA-mediated gene transfection. This single-transformed B7/BB-1+ A431 cell line (but not control A431) functioned as AC for lectin-induced T-cell proliferation, as well as oxidative mitogenesis. This costimulation was dependent on B7/BB-1 expression since the monoclonal antibody BB-1 blocked costimulation of PHA mitogenesis by 75%. After the induction of class II MHC antigen expression by interferon-gamma, B7/BB-1+ KC but not control KC presented alloantigens to resting T-cells in the primary mixed lymphocyte reaction. These data indicate that the stable expression of B7/BB-1 antigen by KC reconstitutes defective AC and alloantigen-presenting activity. The lack of expression of such second signal by normal KC may be responsible for their ability to induce clonal anergy in vitro and in vivo.
[Show abstract][Hide abstract] ABSTRACT: We established a mouse model of cutaneous squamous cell carcinoma (SCC) using the Pam 212 cell line to study antitumor immunity in normal syngeneic hosts. In vitro, Pam 212 cells expressed very low levels of class I major histocompatibility complex (MHC) antigen; interferon-gamma (IFN-gamma) significantly increased the expression of this antigen. In vivo, Pam 212 tumors grew progressively in normal BALB/c hosts and resembled poorly differentiated human cutaneous SCC. Immunization of normal syngeneic hosts with irradiated, class I-negative or -positive Pam 212 cells failed to prevent tumor growth or induce specific cytotoxic T lymphocytes (CTL). However, Pam 212 tumor cells were rejected by C3H allogeneic mice, indicating adequate and functional class I antigen expression in vivo. Rejection of Pam 212 tumors by C3H hosts was in part dependent on CD8+ CTL lysis, as alloreactive anti-H-2d CTL lysed class I-positive Pam 212 cells, demonstrating that Pam 212 cells express functional class I MHC antigens. Both class I-positive and -negative Pam 212 cells were resistant to natural killer cell lysis. We hypothesize that ineffective syngeneic immune responses against Pam 212 cells may involve multiple mechanisms: inability of Pam 212 cells to elicit a primary immune response, as well as resistance to cell-mediated lysis.