Abstract
To increase the effectiveness of anticancer therapy based on immune checkpoint (IC) inhibition, some ICs are being investigated in addition to those used in clinic. We reviewed data on the relationship between PD-L1, B7-H3, B7-H4, IDO1, Galectin-3 and -9, CEACAM1, CD155, Siglec-15 and ADAM17 expression with cancer development in complex with the results of clinical trials on their inhibition. Increased expression of the most studied ICs—PD-L1, B7-H3, and B7-H4—is associated with poor survival; their inhibition is clinically significant. Expression of IDO1, CD155, and ADAM17 is also associated with poor survival, including gastric cancer (GC). The available data indicate that CD155 and ADAM17 are promising targets for immune therapy. However, the clinical trials of anti-IDO1 antibodies have been unsatisfactory. Expression of Galectin-3 and -9, CEACAM1 and Siglec-15 demonstrates a contradictory relationship with patient survival. The lack of satisfactory results of these IC inhibitor clinical trials additionally indicates the complex nature of their functioning. In conclusion, in many cases it is important to analyze the expression of other participants of the immune response besides target IC. The PD-L1, B7-H3, B7-H4, IDO1 and ADAM17 may be considered as candidates for prognosis markers for GC patient survival.
Highlights
Therapy based on inhibition of immune checkpoints (ICs) has become the most promising approach in oncology
The available data indicate that CD155 inhibition is promising as a target for immune therapy
The results considered lead to the conclusion about PD-L1 expression as a candidate for prognostic markers of Gastric cancer (GC) with moderate-risk, an important property of which is the possibility of minimally invasive use
Summary
Therapy based on inhibition of immune checkpoints (ICs) has become the most promising approach in oncology. Increased expression of CD276 has been observed in activated B-cells, T-cells, NK-cells, malignant tumors of the colon, ovary, prostate, pancreas, kidney, squamous cell carcinoma, non-small cell lung cancer, and GC, but is not expressed, or is expressed at a low level, in most normal cells [37,38] This makes it possible to consider CD276 as a promising target for immunotherapy. The results of meta-analyses indicate a relationship between increased expression of CD276 with poor survival in patients with GC and other types of malignant tumors. Among patients with GC and other solid tumors increased B7-H4 expression in tissue, blood, and serum, studied by different methods, including IHC, RTPCR, and ELISA, was associated with a poor prognosis. Inhibition of B7-H4 by mAb FPA150 in clinical study NCT03514121 demonstrated acceptable safety despite B7-H4 expression in many tissues, and some therapeutic effect among B7-H4 expressing tumors [68], indicating that this IC is promising as a therapeutic target
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