Murine Pam 212 cutaneous squamous cell carcinoma is nonimmunogenic in normal syngeneic hosts and resistant to immune effector mechanisms.

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.