Cancer immunotherapy relies on the ability of the immune system to identify and destroy tumor cells and to elicit a long-lasting memory of this interaction. Under ordinary circumstances, however, the ability of tumor cells to trigger an effective immune response is limited. The nominal poor immunogenicity of tumor cells results in part from their weak expression of MHC antigens, adhesion molecules, and costimulatory signals that could allow complete T-cell activation. Tumors may also secrete immunosuppressive molecules, and they often fail to express cytokines that activate local immune responses. These evasive strategies can be overcome by introducing molecules or genes for immune modulation into the cancer immunotherapy.
These immune modulation molecules always contain cytokines and immune checkpoints.
Immune modulation for cancer immunotherapy: Cytokines
Cytokines are molecules made by some immune system cells. They are crucial in controlling the growth and activity of other immune system cells and blood cells. Cytokines are injected, either under the skin, into a muscle, or into a vein. The most common ones are used in cancer immunotherapy are:(1) Interleukins, such as Interleukin-2 (IL-2), which helps immune system cells grow and divide more quickly. A man-made version of IL-2 is approved to treat advanced kidney cancer and metastatic melanoma. (2) Interferons, IFN-alfa, for instance, is used to treat cancer. It boosts the ability of certain immune cells to attack cancer cells. It may also slow the growth of cancer cells directly, as well as the blood vessels that tumors need to grow. (3) Tumour necrosis factor, The interaction of TNF-α with TNF receptor 1 and receptor 2 (TNFR-1, TNFR-2) activates several signal transduction pathways for cancer immunotherapy. (4) Chemokines, CXCL10 and XCL1, which attract CD8+ T cells, NK cells and monocytes, are chemokines used in a number of studies. The intratumoral injection of adenovirus- or plasmid-encoded XCL1 has been combined with a variety of immunotherapies including adoptive transfer of effector T cells delivery of cytokines such as IL-12, or IL-18 and DC vaccine. Together they caused considerable tumor regression or eradicated all tumors, which could include non-injected distant tumors, with a role for CD4+ and CD8+ T cells together with NK cells identified. (5) Hematopoietic growth factors, GM-CSF can funcions by itself, or act as a adjuvant in cancer therapy.
Immune modulation for cancer immunotherapy: Immune checkpoints
The co-stimulatory immune checkpoint molecules can enhance the immune response in cancer immunotherapy, like CD40L, enhance cencer immunotherapy by activating or maturing dendritic cells through ligation of CD40. It is found that immunizing with the vector expressing the costimulatory molecules, like CD80, along with antigen induced higher avidity CD8+ T cells than did immunizing with vector expressing antigen alone.
In cancer immunotherapy, some immune modulation molecules are given by themselves as cancer treatments. Others are used as adjuvants (along with a main treatment) to boost the immune system to improve how well another type of immunotherapy (such as a vaccine) works. Some are used by themselves against some cancers and as adjuvants against others.
Wong K K, et al. Advances in Therapeutic Cancer Vaccines. Advances in Immunology, 2016.
Berzofsky J A, et al. Strategies to use immune modulators in therapeutic vaccines against cancer. Seminars in oncology. WB Saunders, 2012, 39(3): 348-357.