The symphony and its conductor: The multiple and subtle effects of TC-PTP.

Immune response, inflammation, cell proliferation, and cell survival are all functions controlled by various signaling pathways. The combination of these messages, along with the resulting responses, forms a rather complex symphony. Some proteins play a central role in the signaling cascade, much like a skilled conductor directing their musicians. Tyrosine phosphatase proteins, specifically those encoded by the PTPN1 and PTPN2 genes, coordinate the T-cell immune response like small orchestra conductors. One product of these genes, TC-PTP, is a crucial enzyme in regulating cell signaling, especially regarding cell proliferation.

TC-PTP exists in two distinct forms: TC48 is located in the endoplasmic reticulum, while TC45, lacking a hydrophobic tail, is found in the nucleus and cytoplasm (1). This enzyme primarily operates within T cells as an immune checkpoint, negatively regulating the expression of the T-cell receptor (TCR), thus preventing the development of autoimmune diseases (2).

In oncology, TC-PTP is known to have both favorable (by inhibiting oncogenes or activating tumor suppressor genes) and unfavorable (vice versa) impacts (3). Similar to a conductor finely guiding sonata and concerto, the effects of TC-PTP regulation manifest through a multitude of delicate outcomes. Indeed, the consequences of TC-PTP loss of expression vary depending on the type of tumor: it may promote melanoma proliferation while inhibiting colon tumors and glioblastomas (4). TC-PTP is involved in regulating the expression of PD-L1, the ligand of the immune checkpoint molecule PD-1, on cancer cells: reduced TC-PTP expression is associated with increased PD-L1, promoting an immunosuppressive tumor microenvironment (4). Conversely, simultaneous loss of TC-PTP in tumor cells and healthy T cells tends to enhance lymphocyte recruitment and activation, leading to slowed tumor growth (5).

However, in many types of human cancers, TC-PTP is overexpressed. The use of small TC-PTP inhibitory molecules in colorectal and lung cancer cell lines has shown a better response to anti-PD-1 immunotherapy treatments and more effective recruitment of cytotoxic lymphocytes (6). Moreover, these TC-PTP inhibitors are believed to enhance the effectiveness of interferon-gamma (IFN-γ) treatments, thus blocking tumor cell proliferation (6). Phase 1 clinical studies are currently underway with some of these small inhibitory molecules.

Modulating TC-PTP in oncology requires the same finesse as a conductor in the midst of a concerto. To better understand the impact of inhibitors of central molecules in different signaling pathways, such as TC-PTP (7, 8), our various antibodies are available to assist you in your research projects.

Written by
MédiMabs’ Team
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