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Review
. 2022 Dec 10;23(24):15693.
doi: 10.3390/ijms232415693.

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management

Alessia Filippone  1 , Deborah Mannino  1 , Giovanna Casili  1 , Marika Lanza  1 , Irene Paterniti  1 , Salvatore Cuzzocrea  1 , Anna Paola Capra  1 , Lorenzo Colarossi  2 , Dario Giuffrida  2 , Sofia Paola Lombardo  2 , Emanuela Esposito  1
Affiliations
Review

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management

Alessia Filippone et al. Int J Mol Sci. .

Abstract

High-grade brain tumors are malignant tumors with poor survival and remain the most difficult tumors to treat. An important contributing factor to the development and progression of brain tumors is their ability to evade the immune system. Several immunotherapeutic strategies including vaccines and checkpoint inhibitors have been studied to improve the effectiveness of the immune system in destroying cancer cells. Recent studies have shown that kinase inhibitors, capable of inhibiting signal transduction cascades that affect cell proliferation, migration, and angiogenesis, have additional immunological effects. In this review, we explain the beneficial therapeutic effects of novel small-molecule kinase inhibitors and explore how, through different mechanisms, they increase the protective antitumor immune response in high-grade brain tumors.

Keywords: anti-tumor immunity; brain tumors; immune system; protein kinase inhibitor; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunosuppression in brain cancer. The increase of M2 macrophages, activation of microglia and astrogliosis promote a chronic systemic inflammatory environment associated with tumor development and metastasis. In addition, the evasion of the immune system by cancer cells creates an immunosuppressive environment that contributes to tumor growth. The mechanisms of immunosuppression are related to a reduction of the cytotoxic activity of dendritic cells and NK cells and to the increase of cells capable of reducing the activity of CD8+ T-cells such as T-reg and MDSC cells. The figure was created with the help of Biorender.com (accessed on 10 May 2022).
Figure 2
Figure 2
Effects of kinase inhibitors drugs in brain tumors. In brain tumors, inhibition of kinases such as TKR, STK, and NRTK by new molecules significantly reduced the proliferation, migration, and invasion of cancer cells in clinical and preclinical studies. The figure was created with the help of Biorender.com (accessed on 30 May 2022).
Figure 3
Figure 3
Impact of KIs on immune cells in TME. Some KIs through intrinsic mechanisms linked to the blocking of protein kinases, in addition to reducing the growth of cancer cells, can induce anti-tumor immunity. Some KIs mediated anti-tumor immunity through several mechanisms. These include: induction of MCHI molecules which increases the cytotoxic activity of CD8+ T-cells (panel 1), reduction of T-reg (panel 2), and MDSC cells (panel 3), causing an increase in immune cells and a reduction of PD1 expression on lymphocytes, which increases their cytotoxic activity (panel 4). The figure was created with the help of Biorender.com (accessed on 6 September 2022).
See this image and copyright information in PMC

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