Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. VSports app下载.

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

Review
. 2021 Jul 14;13(14):3525.
doi: 10.3390/cancers13143525.

Immunotherapy Strategies for Gastrointestinal Stromal Tumor

Junaid Arshad  1 , Philippos A Costa  2 , Priscila Barreto-Coelho  2 , Brianna Nicole Valdes  3 , Jonathan C Trent  1
Affiliations
Review

Immunotherapy Strategies for Gastrointestinal Stromal Tumor

VSports手机版 - Junaid Arshad et al. Cancers (Basel). .

Abstract

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST VSports手机版. .

Keywords: GIST; antibodies; checkpoint inhibitors; cytokine; gastrointestinal stromal tumors; immunotherapy; lymphocytes V体育安卓版. .

PubMed Disclaimer

Conflict of interest statement (VSports)

The authors declare no conflict of interest.

"V体育ios版" Figures

Figure 1
Figure 1
Immunotherapies in GIST. (A) Cytokine Therapy: Peginterferon alpha-2b is a cytokine-based therapy that is used in combination with imatinib to treat stage III/IV GIST. It functions by presenting an antigen cocktail to an antigen presenting cell (APC) to induce an IL-12 mediated TH1 immune response. The TH1 response secretes interferon-gamma and activates anti-tumoral immune cells. (B–E) Immune Checkpoint Inhibitors: (B) Pembrolizumab, Nivolumab, and Spartalizumab are programmed cell death protein-1 (PD1) inhibitors, preventing the PD1 and PDL1 interaction that leads to immune suppression and evasion of the immune system by cancer cells. (C) Ipilimumab is a CTLA-4 antibody, inhibiting the receptor’s function of sending inhibitory signals to T cells. (D) Epacodostat inhibits indoleamine-2,3-dioxygenase (IDO), an enzyme that decreases immune surveillance by downregulating NK and CD8 cells while upregulating T-regs. (E) Axitinib inhibits VEGF, thereby inhibiting the immunosuppressive function of VEGF. (F) Anti-KIT Antibodies: microtubule destabilizing maytansinoid (LOP628) and SR1 are monoclonal antibodies able to slow the growth of GIST via downregulation of KIT. (G) Cellular Therapy: Anti-KIT chimeric antigen receptor (CAR) T cells bind to GIST tumor cells leading to cell lysis. (H) Bi-specific monoclonal antibodies: binds to a somatostatin receptor (SSTR2) on tumor cells and CD3 to trigger a potent cytotoxic T cell response.
See this image and copyright information in PMC

References

    1. Burch J., Ahmad I. Cancer, Gastrointestinal Stromal (GIST) StatPearls; Treasure Island, FL, USA: 2020.
    1. Costa P.A., Hana C.K.A., Balaji N.C., Skryd A.F., Valdes B.N., Minjares R.O., Barreto-Coelho P., Espejo-Freire A.P., Hakim M.O., Jonczak E., et al. Dose escalation of ripretinib can lead to response in advanced gastrointestinal stromal tumor patients refractory to the standard dose: A report of two cases. Gastrointestinal. Stromal Tumor. 2021;4:1. doi: 10.21037/gist-21-1. - DOI
    1. Nishida T., Blay J.-Y., Hirota S., Kitagawa Y., Kang Y.-K. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. Gastric Cancer. 2016;19:3–14. doi: 10.1007/s10120-015-0526-8. - DOI - PMC - PubMed
    1. Demetri G.D., Von Mehren M., Antonescu C.R., DeMatteo R.P., Ganjoo K.N., Maki R.G., Pisters P.W., Raut C.P., Riedel R.F., Schuetze S., et al. NCCN task force report: Update on the management of patients with gastrointestinal stromal tumors. J. Natl. Compr. Cancer Netw. 2010;8 doi: 10.6004/jnccn.2010.0116. - DOI - PMC - PubMed
    1. Schaefer I.M., Marino-Enriquez A., Fletcher J.A. What is new in gastrointestinal stromal tumor? Adv. Anat. Pathol. 2017;24:259–267. doi: 10.1097/PAP.0000000000000158. - DOI - PMC - PubMed

LinkOut - more resources