Increasing the expression of programmed death ligand 2 (PD-L2) but not 4-1BB ligand in colorectal cancer cells

Autor: Bijan Sedighi Moghadam, Zahra Safaei Naraghi, Mohammad Sadegh Fazeli, Hamid Asadzadeh Aghdaei, Kaveh Baghaei, Kambiz Kamyab Hesari, Maryam Nourizadeh, Raheleh Shokouhi Shoormasti, Parastoo Shakerin
Rok vydání: 2020
Předmět:
Zdroj: Molecular Biology Reports. 47:5689-5697
ISSN: 1573-4978
0301-4851
DOI: 10.1007/s11033-020-05289-7
Popis: Immune checkpoint (ICP) molecules modulate the immune response by either inducing or preventing T cell activation. Over-expression of some ICPs on malignant cells has been shown to regulate anti-tumor immune responses. We aimed to investigate the expression levels of two immune checkpoint molecules which have not been studied extensively in patients with colorectal cancer (CRC). Programmed Death Ligand 2 (co-inhibitory) and 4-1BB ligand (co-stimulatory) were assessed in tumor tissues of CRC patients compared to the adjacent normal tissues. Following tissue excision during surgical operation from 21 CRC patients, RNA extraction, cDNA synthesis and semi-quantitative real-time PCR were done for measuring the expressions of PD-L2 and 4-1BBL genes. In protein level, indirect immunohistochemistery (IHC) was performed on tissue sections. We revealed that PD-L2 was expressed in about 81% CRCs and insignificantly correlated with the tumor differentiation grade. Although a 3.25-fold change in the gene expression of PD-L2 was found in tumor tissues compared to the adjacent normal tissues (P = 0.005), but decreased level of 4-1BBL in counterpart tissues was not significant. Our results were confirmed by IHC for PDL-2 (P = 0.02) and 4-1BBL, however it was not statistically significant for the latter one. Although not significant, we could find an association between the elevated expression of PD-L2 and the tumor differentiation grade. Increased expression of negative regulator of the anti-tumor immune responses like PD-L2, as a prominent way of tumor escape, can be considered for cancer immunotherapy approaches in CRC patients using blocking monoclonal antibodies.
Databáze: OpenAIRE
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