The Features of Checkpoint Receptor-Ligand Interaction in Cancer and the Therapeutic Effectiveness of Their Inhibition.
Anna KuzevanovaNatalya V ApanovichDanzan MansorunovAlexandra KorotaevaAlexander KarpukhinPublished in: Biomedicines (2022)
To date, certain problems have been identified in cancer immunotherapy using the inhibition of immune checkpoints (ICs). Despite the excellent effect of cancer therapy in some cases when blocking the PD-L1 (programmed death-ligand 1) ligand and the immune cell receptors PD-1 (programmed cell death protein 1) and CTLA4 (cytotoxic T-lymphocyte-associated protein 4) with antibodies, the proportion of patients responding to such therapy is still far from desirable. This situation has stimulated the exploration of additional receptors and ligands as targets for immunotherapy. In our article, based on the analysis of the available data, the TIM-3 (T-cell immunoglobulin and mucin domain-3), LAG-3 (lymphocyte-activation gene 3), TIGIT (T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains), VISTA (V-domain Ig suppressor of T-cell activation), and BTLA (B- and T-lymphocyte attenuator) receptors and their ligands are comprehensively considered. Data on the relationship between receptor expression and the clinical characteristics of tumors are presented and are analyzed together with the results of preclinical and clinical studies on the therapeutic efficacy of their blocking. Such a comprehensive analysis makes it possible to assess the prospects of receptors of this series as targets for anticancer therapy. The expression of the LAG-3 receptor shows the most unambiguous relationship with the clinical characteristics of cancer. Its inhibition is the most effective of the analyzed series in terms of the antitumor response. The expression of TIGIT and BTLA correlates well with clinical characteristics and demonstrates antitumor efficacy in preclinical and clinical studies, which indicates their high promise as targets for anticancer therapy. At the same time, the relationship of VISTA and TIM-3 expression with the clinical characteristics of the tumor is contradictory, and the results on the antitumor effectiveness of their inhibition are inconsistent.
Keyphrases
- poor prognosis
- binding protein
- papillary thyroid
- cancer therapy
- randomized controlled trial
- systematic review
- big data
- end stage renal disease
- cell therapy
- electronic health record
- newly diagnosed
- mental health
- chronic kidney disease
- squamous cell
- ejection fraction
- prognostic factors
- cell cycle
- small molecule
- machine learning
- cell proliferation
- long non coding rna
- bone marrow
- dna methylation
- young adults
- protein protein
- artificial intelligence
- patient reported outcomes
- deep learning