Volume 1: Strategies for Therapeutic Cancer Vaccine Development deals with different strategies of cancer vaccine development, focusing on techniques for the development of therapeutic cancer vaccines and the roles of tumor antigens, proteins/peptides, microbial genes, and stem cells for the development of vaccines for cancer management. Volume 2: Delivery Strategies for Cancer Vaccine and Immunotherapy in Management of Various Carcinomas covers delivery strategies of cancer vaccines for the management of various forms of carcinoma, examining the prospects of delivering immuno-oncology therapies, focusing specifically on the effective drug delivery strategies for treatment of lung, prostate, and pancreatic carcinomas.

With their unprecedented success, cancer immunotherapies including immune checkpoint inhibitors (ICIs), cancer vaccines, adoptive cell therapy (ATC), and immunomodulators are being increasingly used for various malignancies. Distinct from traditional treatments including surgery, radiation therapy, and chemotherapy, immunotherapeutics attempt to create long-lasting anti-tumor effects. However, only a minority of patients experience long-term benefits to single-agent immunotherapy, and most patients do not have initial responses to the immunotherapy or develop relapse after promising initial responses. Strategies to overcome immunotherapy resistance include (1) the development of biomarkers to select potential responders and/or exclude potential non-responders; and (2) the usage of combination treatments (ICIs, radiotherapy, chemotherapy, vaccines, fecal microbiota transplantation (FMT) and etc.) comprising different mechanisms of action and target multiple resistant mechanisms. At the same time, the possibility of new side effects due to the combinatorial strategies or the potential amplification of the well-known side effects of the ICIs, termed immune-related adverse events (irAEs), should be carefully monitored.

The tumor microenvironment (TME) plays a critical role in tumor proliferation, progression, and therapeutic responses. TME is a complex network of cancer cells, stromal cells, and, most importantly, infiltrating immune cells. Cancer cells regulate numerous biological functions through direct or indirect interaction with TME components. Emerging evidence suggests that TME crucially influences the response to both chemotherapy and immunotherapy. As scientific research has entered the big data era with the fast development of high-throughput sequencing technologies, machine learning has been gradually widely applied to extract important knowledge from big data bioinformatics. Thus, characterizing the TME landscape in cancer and identifying different immune-related TME phenotypes using machine learning-based bioinformatics analyses, in vitro experiments, and in vivo experiments are of great interest and significance.

Cancer immunotherapy is based on using the immune system components to fight tumors, without destroying normal cells. Several immunotherapeutic strategies have been investigated and proposed for the treatment of cancers, including cancer vaccines containing tumor antigens that are used to induce immune responses against tumors, monoclonal antibodies against tumor antigens, and immune checkpoint inhibitors. However, many clinical trials have shown that the use of these methods as monotherapy is ineffective in many cases. Many tumors can resist immunotherapy due to the absence or insufficient infiltration of tumors with CD8+ T cells and hence, are called “cold” or non-inflammatory tumors. Cold tumors are characterized by a lack of infiltrating CD8+ T cells, the presence of anti-inflammatory myeloid cells, tumor-associated M2 macrophages, and regulatory T cells. A combination of other cancer therapeutic approaches, such as chemotherapy or immunotherapy with cancer vaccines, could dramatically enhance the efficacy and, eventually, the outcome of the treatment. Despite some success of the immunotherapy of oncological diseases, cold tumors represent one of the main therapeutic challenges for modern immunotherapy. It can be expected that in the near future, treatment algorithms will be developed to adapt the therapeutic strategies to the immune context of the tumor since treatment with checkpoint inhibitors or vaccines alone is not enough for cold tumors. Therefore, using other therapeutic approaches alongside the existing treatment methods can be more reasonable for cold tumors that do not strongly stimulate the immune system or resist against it. To apply targeted treatments such as the use of small molecules, small peptides, hybrid small molecules, biologically active peptides, non-protein isolates of food products or by-products, and every material that is capable of the disturbing immunosuppressive tumor microenvironment (TME) as an adjuvant therapy can reduce the resistance of cold tumors to immunotherapy which is so-called turning them into “warm” tumors. This research topic aims to cover all outstanding advances in immunology, medical chemistry and biochemistry, pharmacology, food engineering and molecular biology of contemporary molecular drug targets involved in cancer treatment and encompasses the following subjects: • Definition and explanation of cold tumors and challenges ahead toward their treatment • Designing and application of small peptides, small molecules, and other similar materials to overcome suppressive TME and break tumors resistance • Extraction and preparation of bioactive peptides or other components derived from natural resources to make cold tumor barriers fragile • Modifications and alterations leading to overcoming cold tumor resistance against cancer vaccines and ICP inhibitors Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

This volume will describe recent progress and future directions in radiation oncology and biology research, focusing on strategies designed to improve disease control and reduce the risk of long-term adverse effects on patients. As more and more patients are becoming long-term survivors, this strategy will become increasingly important--in radiation oncology and throughout the field of oncology.