Anti-tumor immunological response induced by cryoablation and anti-CTLA-4 antibody in an in vivo RM-1 cell prostate cancer murine model

Abstract

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible.

Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells

“…5A and B). Compared with PBS-injected mice, anti-CTLA-4 suppressed tumour growth in two mice models, which is supported by previous observations (24). In addition, residual ALDH + MSCs were observed within the tumour.…”

Cytotoxic T Lymphocyte Antigen-4 Down-Regulates T Helper 1 Cells by Increasing Expression of Signal Transducer and Activator of Transcription 3 in Acute Graft-versus-Host Disease

“…As the costimulatory molecule of T cells, CTLA-4 is the second signal, which mainly regulates T cell activation. CTLA-4 also has been documented to play an important role in the progress of anti-tumor [8][9][10] and anti-infection [11][12][13] responses, as well as some autoimmune diseases, including polymyositis [14] and systemic lupus erythematosus [15].…”

Immune checkpoints in aggressive breast cancer subtypes

“…CTLA-4 is operational during early activation of T naïve cells in lymphatic tissues. One of the typical features of CTLA-4 blockade is the durability of objective tumor response [4,6,7]. PD-1 (programmed cell death protein 1, also known as cluster of differentiation CD279)-is an immune inhibitory receptor expressed on the surface of activated T cells, B cells, natural killers and macrophages and it has two ligands PD-L1 and L2.…”