Increasing the expression of programmed death ligand 2 (PD-L2) but not 4-1BB ligand in colorectal cancer cells
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ORIGINAL ARTICLE
Increasing the expression of programmed death ligand 2 (PD‑L2) but not 4‑1BB ligand in colorectal cancer cells Parastoo Shakerin1,2 · Bijan Sedighi Moghadam2 · Kaveh Baghaei1 · Zahra Safaei Naraghi3 · Kambiz Kamyab Hesari3 · Hamid Asadzadeh Aghdaei1 · Raheleh Shokouhi Shoormasti4 · Mohammad Sadegh Fazeli5 · Maryam Nourizadeh4 Received: 15 October 2019 / Accepted: 28 January 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords Immune checkpoint molecules · Programmed death ligand 2 (PD-L2) · 4-1BB ligand
Introduction Parastoo Shakerin and Bijan Sedighi Moghaddam contributed equally as the first author. * Maryam Nourizadeh [email protected] 1
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
3
Department of Dermatopathology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
4
Immunology, Asthma, & Allergy Research Institute, Tehran University of Medical Sciences, Tehran 1419733151, Iran
5
Department of Surgery, School of Medicine. Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
Colorectal cancer (CRC) is known as the third diagnosed cancer and the fourth leading
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