Inflammation Control and Immunotherapeutic Strategies in Comprehensive Cancer Treatment

HIGHLIGHTS: 1. Tumor progression and regression are determined by immunological properties of the tumor microenvironment. 2. Tumor is capable of generating tumor-protective inflammation. 3. Immunotherapy should upregulate tumor-inhibiting immunity and/or downregulate tumor-promoting immunity. 4. Anti-cancer therapy for advanced disease should ensure long-term tumor cell/mass dormancy, rather than tumor elimination. 5. C-reactive protein, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio are important prognostic markers for cancer development. ABSTRACT: Tumor growth and expansion are determined by the immunological tumor microenvironment (TME). Typically, early tumorigenic stages are characterized by the immune system not responding or weakly responding to the tumor. However, subsequent tumorigenic stages witness the tumor promoting its growth and metastasis by stimulating tumor-protective (pro-tumor) inflammation to suppress anti-tumor immune responses. Here, we propose the pivotal role of inflammation control in a successful anti-cancer immunotherapy strategy, implying that available and novel immunotherapeutic modalities such as inflammation modulation, antibody (Ab)-based immunostimulation, drug-mediated immunomodulation, cancer vaccination as well as adoptive cell immunotherapy and donor leucocyte transfusion could be applied in cancer patients in a synergistic manner to amplify each other’s clinical effects and achieve robust anti-tumor immune reactivity. In addition, the anti-tumor effects of immunotherapy could be enhanced by thermal and/or oxygen therapy. Herein, combined immune-based therapy could prove to be beneficial for patients with advanced cancers, as aiming to provide long-term tumor cell/mass dormancy by restraining compensatory proliferation of surviving cancer cells observed after traditional anti-cancer interventions such as surgery, radiotherapy, and metronomic (low-dose) chemotherapy. We propose the Inflammatory Prognostic Score based on the blood levels of C-reactive protein and lactate dehydrogenase as well as the neutrophil-to-lymphocyte ratio to effectively monitor the effectiveness of comprehensive anti-cancer treatment.