Cancer immunotherapy of Wilms tumor: a narrative review

Abstract

Wilms tumor (WT) is the most common malignant tumor of the urinary system in children. Though the traditional treatment of surgery plus radiotherapy and chemotherapy achieves exciting clinical efficacy, in relapsed and refractory cases, the long-term overall survival rates are poor. Besides, chemotherapy and radiation have serious long-term toxic side effects on children. Cancer immunotherapy is a new tumor therapy that works by activating the body's immune system to allow immune cells to kill tumor cells more efficiently. Currently, cancer immunotherapy has been tested in clinical trials or basic studies in WT. This article reviews the current status of clinical trials and basic research of cancer immunotherapy in WT to promote the application of cancer immunotherapy in WT patients.

Keywords: Wilms tumor; cancer immunotherapy; immune cell therapy; immune checkpoint; therapeutic tumor vaccine.

Figure 1.

Mechanism of therapeutic tumor vaccine killing tumor cells. After the vaccine is injected subcutaneously, the antigen enters the lymph nodes through the lymphatic vessels. Then the antigen-presenting cells in the lymph nodes phagocytose the vaccine antigens and present them to the CTLs. The CTLs are activated and become antigen-specific CTLs. After antigen-specific CTLs enter the tumor tissue, they recognize the tumor cells which have the same or similar antigen as the vaccine and then secrete perforin and granzyme to kill the tumor cells under the help of the combination of TCR with MHC-antigen complex and CD80 with CD28.

Figure 2.

Mechanism of immune checkpoint inhibitors working in tumor treatment. After contact between CTLs and tumor cells, CTLs can't be activated in the condition of combining the immune checkpoint proteins PD-1 with PD-L1 and CD80 with CTLA4, leading to tumor immune escape. After using immune checkpoint inhibitors such as anti-PD1 antibodies, anti-PD-L1 antibodies or anti-CTLA4 antibodies, these immune checkpoint inhibitors bind to the immune checkpoint proteins on the membrane of a tumor cell or TCL, thus relieving the inhibition of CTL so that CTL can secrete granzyme and perforin to kill tumor cells.

Figure 3.

Mechanism of CAR-T killing the tumor. When CAR of CAR-T cells recognizes and binds with the specific antigen of the tumor cell membrane, CAR-T is activated and releases granzyme and perforin killing tumor cells without needing the combination of TCR and antigen-MHC complex. CAR-T: Chimeric antigen receptor T cells; MHC: Major histocompatibility complex.

Figure 4.

TAA-T cell production process and mechanism of killing tumor cells. First, T lymphocytes and DC cells were isolated from 100 ml of patients' venous peripheral blood. Then T lymphocytes, DC cells and tumor-specific antigens were co-cultured in vitro. During the process, co-cultured T cells were trained by DC became to TAA-T. TAA-T can specifically recognize and kill tumor cells expressing the co-cultured antigen after entering the patient body. The killing mode is that the TCR of TAA-T cells recognizes specific antigens-MHC complex on the tumor cell membrane and then activates TAA-T with the assistance of binding costimulatory molecules to release granzyme and perforin to kill tumor cells.