Cancer Vaccine in Cold Tumors: Clinical Landscape, Challenges, and Opportunities

The idea of cancer immunotherapy is to stimulate the immune system to fight tumors without destroying normal cells. One of the anticancer therapy methods, among many, is based on the use of cancer vaccines that contain tumor antigens in order to induce immune responses against tumors. However, clinical trials have shown that the use of such vaccines as monotherapy is ineffective in many cases since they do not cause a strong immune response. Particular tumors are resistant to immunotherapy due to the absence or insufficient infiltration of tumors with CD8+ T cells, and hence, they are called cold or non-inflamed tumors. Cold tumors are characterized by a lack of CD8+ T cell infiltration, the presence of anti-inflammatory myeloid cells, tumor-associated M2 macrophages, and regulatory T cells. It is very important to determine the stage of the antitumor response that does not work properly in order to use the right strategy. Applying other therapeutic methods alongside cancer vaccines can be more rational for cold tumors, which do not provoke the immune system strongly. Herein, we indicate some combinational therapies that have been used or are in progress for cold tumor treatment alongside vaccines.