Immunologic Tumor Microenvironment Modulators for Turning "Cold" Tumors to "Hot" Tumors

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Background

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.

Keywords: Cold tumor, Small peptide, Small molecule, Bioactive Peptide, Cancer vaccine, Immune check-point inhibitor

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