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

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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.

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Acknowledgements

We would like to thank Samaneh Tokhan Beigi for her technical assistant and Dr. Behboo and Dr. Farzaneh Niknafs for collecting the samples. Also, we would like to appreciate all the patients who participated in this study. This work was supported by the Gastroenterology and Liver Diseases Research center, Research institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Funding

Semnan University of Medical Science (code:1134).

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Author notes

  1. Parastoo Shakerin and Bijan Sedighi Moghaddam contributed equally as the first author.

Authors and Affiliations

  1. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Parastoo Shakerin, Kaveh Baghaei & Hamid Asadzadeh Aghdaei

  2. Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Parastoo Shakerin & Bijan Sedighi Moghadam

  3. Department of Dermatopathology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Zahra Safaei Naraghi & Kambiz Kamyab Hesari

  4. Immunology, Asthma, & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, 1419733151, Iran

    Raheleh Shokouhi Shoormasti & Maryam Nourizadeh

  5. Department of Surgery, School of Medicine. Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Sadegh Fazeli

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  1. Parastoo Shakerin
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  2. Bijan Sedighi Moghadam
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Correspondence to Maryam Nourizadeh.

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Shakerin, P., Sedighi Moghadam, B., Baghaei, K. et al. Increasing the expression of programmed death ligand 2 (PD-L2) but not 4-1BB ligand in colorectal cancer cells. Mol Biol Rep 47, 5689–5697 (2020). https://doi.org/10.1007/s11033-020-05289-7

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  • DOI: https://doi.org/10.1007/s11033-020-05289-7

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