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The introduction of immune checkpoint inhibitors represented a true revolution in the treatment of melanoma and a few other cancer subtypes. Unfortunately, the use of these drugs did not achieve the same beneficial results in other neoplasms, such as soft tissue sarcoma and gastrointestinal stromal tumor. These failures encouraged deeper research into the complex interactions between cancer and host immune system, to try to shed light on the ability of cancer cells to escape immunologic surveillance. Key elements to explain tumor immune escape were found in the tumor microenvironment. The main actors in this complex network are lymphocytes, cytokines and innate immunity cells such as macrophages and antigen presenting cells. Thus, immuno-oncologists are studying the different components of the tumor microenvironment to identify possible new therapeutic targets. In this paper, we summarize the most important aspects of these interactions, and provide an overview of the newer and more promising immunotherapeutic strategies.

Background Pazopanib is a multikinase inhibitor registered for the treatment of advanced renal clear cell carcinoma (RCC) and as second or further-line therapy in advanced non-adipocytic soft tissue sarcoma (STS). It is a relatively well-tolerated compound, but, as with many other tyrosine kinase inhibitors (TKI), chronic toxicity may become a challenge that both patient and physician need to take into account when starting treatment. This retrospective study investigated toxicities and their management in STS patients treated with pazopanib in routine clinical practice in Italy. Materials and Methods Data were collected between January 2013 and May 2016 at Candiolo Cancer Institute and Prato Medical Oncology Unit. The primary objective was to describe observed toxicities in a real-life setting, and use this information to inform strategies for adverse event management. Results A total of 43 patients with advanced STS who received treatment with pazopanib were included. Median progression-free survival was 4 months and median overall survival was 18 months. The most common toxicities were fatigue (74.4%), hypertension (72%), hair hypopigmentation (74.4%) and diarrhea (60.5%). Liver toxicities occurred in less than one-third of patients. Severe adverse events, requiring drug interruption, were relatively rare. Conclusions This study confirms the safety and efficacy of pazopanib in pretreated unresectable or metastatic soft tissue sarcoma, and highlights the importance of close follow-up and patient support to improve compliance and treatment duration.