New Approaches on Cancer Immunotherapy

Abstract

Metastasis, which occurs when cancer cells disseminate from the primary tumor site to other parts of the body, is the primary cause of mortality in patients, and the recurrence of multiple metastatic tumors is an obstacle to eliminating cancer. Recent clinical studies demonstrated that patients who respond to immunotherapy have longer survival rates with lower metastatic relapse, suggesting that immunotherapy may be one of the solutions to overcome cancer metastasis. Indeed, various host immune cells not only shape the tumor microenvironment but also participate in multiple stages of metastasis. Therefore, to improve clinical outcome, it is critical to understand the immunological events associated with tumor development and progression. In this article, we summarize those events that are involved in tumor progression and discuss immunotherapies that can potentially target cancer metastasis.

Figure 1.

Immune response during tumor development. (A) The processes of tumor development. (B) The processes of immune response in tumor formation. (NK) natural killer cell, (Mφ) macrophages, (TH1) type 1 helper T cells, (CTL) cytotoxic T lymphocytes, (DC) dendritic cells, (MHC) major histocompatibility complex, (APM) antigen processing and presentation machinery, (gMDSCs) granulocytic myeloid-derived suppressor cells, (ECM) extracellular matrix, (TME) tumor microenvironment, (TMEM) tumor microenvironment of metastasis, (TNFα) tumor necrosis factor alpha, (INFγ) interferon gamma, (TGF-β) transforming growth factor beta, (IL-12) interleukin-12, (T regs) regulatory T cells, (PD-L1) programmed death-ligand 1, (Gal-9) galectin-9, (CD80) B-lymphocyte activation antigen B7, (CD86) B-lymphocyte activation antigen B7-2.

Figure 2.

Perspectives in cancer immunotherapy. The conversion of “cold” tumor (low TIL population) to “hot” tumor (high TIL population) has the potential to improve the efficacy of current immune therapy. Various approaches to establish a TME that is friendly to T-cell immunity may be considered, such as by combining current ICB and ACT therapy.