ABSTRACT
OBJECTIVE: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) in anal cancer. PATIENTS AND METHODS: In a retrospective cohort analysis, subjects with squamous cell carcinoma of the anal canal were tested for PD-L1 expression, then followed for recurrence and survival. Crude recurrence rates (CRRs), crude mortality rates (CMRs), and crude event rates (CERs) were assessed for PD-L1-dependent differences using Poisson regression. All 3 types of crude rate were expressed as the number that occurred per hundred person-years (hPY) of follow-up. RESULTS: Samples from 41 subjects were evaluated for PD-L1 expression; 23 (56%) were positive. Subjects with PD-L1-expressing versus PD-L1-negative tumors respectively had CRRs of 30.8 versus 12.1 recurrences/hPY (P=0.082), CMRs of 16.7 versus 12.0 deaths/hPY (P=0.47), and CERs of 39.2 versus 16.9 events/hPY (P=0.069). CONCLUSIONS: PD-L1 positivity was associated with worse CRR and CER, and marginally worse CMR. The effect on progression-free and overall survival needs to be validated in a study with a larger sample size.
Subject(s)
Anus Neoplasms/pathology , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/pathology , Neoplasm Recurrence, Local/pathology , Adult , Aged , Aged, 80 and over , Anus Neoplasms/metabolism , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/therapy , Prognosis , Retrospective Studies , Survival RateABSTRACT
The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/ß-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines.
ABSTRACT
BACKGROUND: Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. METHODS: A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. RESULTS: A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. CONCLUSION: Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer.
