Comparison of in vivo and in vitro prostaglandin E2 production by squamous cell carcinoma of the head and neck.

Prostaglandin E2 has been identified as an immunosuppressive factor in patients with squamous cell carcinoma of the head and neck. Spontaneous prostaglandin E2 production by 21 cancer cell lines, which were obtained from 17 patients with squamous cell carcinoma of the head and neck, was determined by radioimmunoassay. In comparison with normal keratinocyte cultures, prostaglandin E2 production by cancer cell lines was significantly decreased (p < 0.0001). Prostaglandin E2 levels demonstrated no correlation to the site, stage, or histopathologic differentiation of the tumor. In a separate group of 17 patients with squamous cell carcinoma of the head and neck, tumor cells were isolated from fresh tumor specimens, and 24-hour PGE2 production in vitro was assayed. No correlation was found with tumor site, stage, or 2-year disease-free survival. Although prostaglandin E2 may have biologic significance in vivo in patients with squamous cell carcinoma of the head and neck, these findings suggest that measurements of tumor cell-derived prostaglandin E2 are not predictive of biologic behavior.

T-cell markers in tumor-infiltrating lymphocytes of head and neck cancer.

Fresh suspensions of tumor-infiltrating lymphocytes (TIL) from 16 patients with squamous cell carcinoma of the head and neck (SCCHN) were examined for T-cell markers including CD4 (helper-inducer), CD8 (cytotoxic-suppressor), natural killer (NK) cell, and activation surface markers using monoclonal antibodies and two-color flow cytometry. Two of 8 (25%) patients with a CD4/CD8 ratio of less than 1 developed cervical lymph node metastases; none had extracapsular spread. Six of 8 (75%) patients with a CD4/CD8 ratio of greater than 1 developed cervical metastases; 5 of 6 (83%) exhibited extracapsular spread. An increased CD4/CD8 ratio was attributable to a decrease in CD8+ cells. A CD4/CD8 ratio of greater than 1 may be a useful prognostic indicator of the development of cervical metastases.

Characterization of novel anti-tumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes.

TIL were isolated from human solid tumors and cultured in rIL 2. Long-term TIL lines from primary tumors showed a shorter lag period, better expansion, and higher anti-tumor activity in vitro than those from metastatic tumors. The anti-tumor effector cells in TIL and A-PBL cultures had CD3+ Leu 19+ and CD3- Leu19+ phenotypes and morphology consistent with LGL/LAK cells. These cells mediated lysis of both autologous and allogeneic fresh tumor cell targets, while CD3+ Leu19- cells had little or no antitumor cytotoxicity.

Cytolytic antitumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes in recombinant interleukin 2.

Lymphocytes infiltrating human solid tumors (TIL) and autologous peripheral blood lymphocytes (A-PBL) were cultured with 1000 units/ml of recombinant interleukin 2 (rIL2) in long-term cultures. TIL isolated from 26 primary squamous cell carcinomas of the head and neck expanded better (P less than 0.01) and achieved higher total lytic units of activity against fresh tumor cell targets (P less than 0.05) than A-PBL. TIL obtained from primary hepatocellular carcinomas (n = 7) showed a higher degree of expansion than those from metastatic liver tumors (n = 7). Further, TIL from metastatic tumors of the head and neck, liver, and ovary were delayed up to 50 days in their proliferative response to rIL2. Long-term mass cultures in rIL2 of TIL, A-PBL, or normal PBL were serially monitored for cytotoxicity with different cultured and fresh tumor cell targets and for phenotypic markers of the predominating cell populations. Antitumor cytotoxicity was found in cultures enriched in CD3+Leu19+ and/or CD3-Leu19+ cells. Two-color sorting of such cultures followed by cytotoxicity assays confirmed that the human antitumor effectors expressed either the CD3+Leu19+ or CD3-Leu19+ phenotype. CD3+Leu19- cells had little or no antitumor cytotoxicity. The two types of Leu19+ effector cells were present in low numbers in fresh TIL, A-PBL, or normal PBL; in contrast, in some rIL2-expanded long-term cultures, they represented a majority of proliferating cells. This study identifies for the first time two types of antitumor effector cells in rIL2 cultures of human TIL, one of which may represent activated natural killer cells on the basis of the absence of the CD3 and expression of the Leu19 antigen. These antitumor effector cells mediate non-MHC-restricted cytotoxicity of fresh or cultured tumor cell targets of different histologic types.