ABSTRACT
Background: The PD-1/PD-L1 signaling axis is currently the most elucidated mechanism for tumor evasion of T-cell-mediated immunity. Nevertheless, few data are available regarding its impact on cervical cancer and the relationship with lymphocytic infiltrates. Methods: A retrospective assessment of all cases of cervical neoplasia treated in Caxias do Sul General Hospital, Brazil, between 2012 and 2016 was performed. Clinical and pathological data were collected from electronic records and analyzed. Original slides were independently reviewed by three pathologists to confirm diagnoses and to assess the immunohistochemical expression of PD-L1 and FoxP3 in tumor cells and lymphocytic infiltrates. Results: PD-L1 staining was present in 32.2% of the 59 cervical samples. Median overall survival time of the PD-L1-negative group was 47.8 months, a time point not yet reached by the PD-L1-positive group (p=0.968). Median progression-free survival was 24.3 months for PD-L1-negative and 11.5 months for PD-L1-positive patients (p=0.263). PD-L1 staining was found in 27.1% of the lymphocytic infiltrates, and survival analysis revealed no difference between PD-L1-positive and PD-L1-negative samples. There was no impact on survival related to FoxP3 staining in neither tumor samples nor lymphocytic infiltrates. Conclusion: Although the median progression-free survival times differed, the difference was not statistically significant. Our study corroborates the rationale that PD-L1 expression in cervical neoplasms has no impact on survival. PD-L1 expression in peritumoral lymphocytes revealed no impact on infiltration volume nor survival. Keywords: uterine cervical neoplasms, tumor-infiltrating lymphocytes, cancer, tumor microenvironment, survival.
ABSTRACT
Thalidomide has anti-angiogenic and immunomodulatory activity, exhibiting antitumour effects in patients with multiple myeloma and, more rarely, in several other solid tumours. We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels]. A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients. Thalidomide was given orally at a daily dose of 200 mg/day, which was then escalated every 2 weeks by 200 mg/day as tolerated to a maximum of 800 mg/day. Patients were evaluated every 8 weeks for response using the World Health Organization (WHO)-27 criteria. Fourteen patients were enrolled and no objective responses were observed, with one stable disease and one mixed response. The dose-limiting toxicities were constipation, dizziness and somnolence. Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor and fatigue. The plasma pharmacokinetics of thalidomide were comparable with those of previous studies in normal volunteers and in patients with advanced prostate cancer. Serum levels of b-FGF and VEGF did not change significantly following drug administration. In conclusion, thalidomide showed poor activity, but acceptable toxicity, in patients with metastatic melanoma. Future studies should explore this agent in combination with other biological agents or cytotoxic agents, such as temozolomide.