Tumor Interstitial Fluid as Modulator of Cancer Inflammation, Thrombosis, Immunity and Angiogenesis

Tumor interstitial fluid (TIF) is a watery phase that accumulates inside the tumor interstitium. Its genesis and fate depend on various factors, namely tumor type, metabolic state of the tumor, expression of vascular endothelial growth factor, and absence of lymphatic system. For almost 30 years TIF remained a neglected entity until it was demonstrated that TIF, and in particular its high pressure, constitutes an important obstacle to drug delivery and immunotherapy. The present review not only summarizes the abundant literature on the processes of TIF genesis and on its effects on therapy but it also presents data that, in our opinion, point towards what is perhaps the real physiological purpose of the TIF: a primitive means of providing nourishment, oxygen, cytokines and matrikines to tumor cells that furthermore promotes the invasion of the normal surrounding tissue and passive metastatization through lymphatics. It is also an inducer of inflammation through increased osmolarity due to albumin loss. Recently, a role for TIF as a possible source of biomarkers has also been suggested

Update on the challenges and recent advances in cancer immunotherapy

Gianfranco Baronzio,1 Gurdev Parmar,2 Irina ZH Shubina,3 Valter Cassutti,1 Sergio Giuli,1 Marco Ballerini,1 Mikhail Kiselevsky3 1Centro Medico Demetra: Hyperthermia and Immunity Center, Terni, Italy; 2Integrated Health Clinic, Fort Langley, British Columbia, Canada; 3Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia Abstract: This overview provides an analysis of some of the immunotherapies currently in use and under investigation, with a special focus on the tumor microenvironment, which we believe is a major factor responsible for the general failure of immunotherapy to date. It is our expectation that combining immunotherapy with methods of altering the tumor microenvironment and targeting regulatory T cells and myeloid cells will yield favorable results. Keywords: tumor microenvironment, tumor immunity, immunosuppression, CTLA-4, PD-1, exosomes, myeloid-derived suppressor cells, Treg