ABSTRACT
Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.
Subject(s)
Immunotherapy/methods , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Influenza Vaccines/therapeutic use , Injections, Intralesional , Neoplasms/drug therapy , Neoplasms/immunology , Adjuvants, Immunologic/administration & dosage , Animals , B-Lymphocytes , Basic-Leucine Zipper Transcription Factors/genetics , CD8-Positive T-Lymphocytes/immunology , Humans , Immunity, Cellular , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human , Interleukin-10 , Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Mice , Mice, Inbred C57BL , Repressor Proteins/genetics , Seasons , Skin , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Squalene/administration & dosage , Tumor Microenvironment/drug effects , VaccinationABSTRACT
BACKGROUND: Laparoscopic cholecystectomy is the treatment of choice for biliary dyskinesia; however, long-term outcomes remain unclear. METHODS: A retrospective review of patients diagnosed with biliary dyskinesia and treated with laparoscopic cholecystectomy at a single institution between 2001 and 2012 was conducted. Long-term outcome data were obtained by telephonic interview using a modified Likert scale. RESULTS: Sixty-seven patients met inclusion criteria, of which 34 patients (51%) had long-term follow-up data. Mean time of follow-up was 65 (range: 6 to 134) months. Long-term follow-up demonstrated symptom response in 88% (n = 30) of patients (responders), compared to no response in 12% (n = 4) of patients (nonresponders). Responders underwent a mean of 1.56 preoperative diagnostic procedures, compared to 2.5 for nonresponders (P = .01). CONCLUSION: This represents the longest mean time of follow-up study demonstrating the success of laparoscopic cholecystectomy to improve symptoms in patients with biliary dyskinesia.
