Oral squamous carcinoma cells promote macrophage polarization in an MIF-dependent manner.

BACKGROUND: Tumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoangiogenesis, extracellular matrix remodeling and dysregulated tumor cell proliferation. Our prior studies revealed that macrophage-derived, but not tumor cell-derived, macrophage migration inhibitory factor (MIF), is an important determinant of TAM alternative activation and M2 polarization. AIM: Because MIF is historically thought to initiate signaling via a receptor-dependent, outside-in mode of action, we wished to investigate the specific contributions of tumor-derived vs. macrophage-derived MIF to M2 marker expression during macrophage polarization. DESIGN: Murine oral squamous cell-carcinoma cells (SCCVII) were co-cultured with either the RAW 264.7 mouse macrophage cell line or mouse primary bone marrow-derived macrophages in the context of MIF genetic loss/inhibition individually or in combination each cell type. METHODS: Twelve well Transwell plates were used to co-culture SCCVII cells and RAW 264.7, MIF+/+ or MIF-/- macrophages treated with/without the small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine and incubated in the presence or absence of interleukin (IL-4) for 48 h. Macrophages were analyzed by quantitative real-time polymerase chain reaction and/or immunoblotting for relative macrophage polarization marker expression. RESULTS: IL-4 treatment synergizes with SCCVII co-culture in inducing the expression of macrophage M2 markers and loss or inhibition of macrophage-derived MIF significantly reduces both IL-4 alone and IL-4/SCCVII co-culture-induced macrophage M2 marker expression. CONCLUSION: These studies identify an important and dominant requirement for macrophage MIF in maximal Th2-cytokine and oral squamous carcinoma cell-induced macrophage polarization and M2 marker expression.

Therapeutic association for nasopharyngeal cancer.

The authors studied retrospectively 16 cases of malignant epithelial nasopharyngeal tumors which were treated at the Head and Neck Service of the Heliópolis Hospital, São Paulo, Brasil, from December 1977 to December 1983. The treatment was intra-arterial chemotherapy (IAC) followed by radiotherapy. The chemotherapeutic schedules were: methotrexate and vincristine, methotrexate, bleomycin and vincristine (2 different schedules) and methotrexate, bleomycin, vincristine and cisplatinum. Objective responses to IAC were observed in 18.6% of the cases. Only 3 patients are alive at 26, 37 and 53 months; 2 of them had exhibited response to IAC. The authors analyze the results and suggest randomized trials in order to determine the exact effects of this method of treatment.

Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx.

BACKGROUND: The extracapsular spread of disease in modal metastasis of head and neck tumors is an important prognostic factor. However, the implications of the degree of capsular involvement are rarely mentioned. This is a prospective study which intends to investigate the role of transcapsular spread in metastatic lymph nodes on the outcome of patients with laryngeal or hypopharyngeal carcinoma. METHODS: This is a prospective study of 170 consecutive cases of previously untreated patients with squamous cell carcinoma of the larynx or the hypopharynx treated from January 1981 through January 1988 at the Head and Neck Service of the Heliópolis Hospital Complex, São Paulo, Brazil. In an attempt to understand better the influence of the extension of capsular lymph node involvement on recurrence and actuarial survival rates, the Kaplan-Meier method and Mantel-Cox test were used. RESULTS: The nodal cervical relapse was associated only to a macroscopic transcapsular spread (confidence interval, 1.7-7.0). When the carcinoma was confined to the lymph node or only a microscopic transcapsular spread was present, no statistically significant differences were found in recurrence or in death rates. The 5-year global and disease-free actuarial survival rates were, respectively, 52.0% and 56.8% for cases without metastasis and 5.8% and 10.2% when macroscopic transcapsular spread was present (p < .0001). The capsular rupture was the most important independent prognostic factor associated with the N categories of the TNM clinical classification and with metastatic lymph node diameter. CONCLUSIONS: The risks of recurrence and death are higher when there is macroscopic extracapsular extension. When the tumor is confined to the lymph node or shows a microscopic invasion beyond the capsule, there are no statistically significant differences in risk rates. The risk of capsular rupture is related to the N category of the classification TNM and the diameter of the metastatic lymph node, from 3 cm and larger.