en Clinical Neuroscience Clinical Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Primary Diffuse Large B Cell Lymphoma of CNS (PCNSL) is a rare variant of Diffuse Large B Cell Lymphoma (DLBCL) and presents with an aggressive clinical course and usually resistant to commonly used therapy regimens. Recently, role of immune checkpoint molecules including PD-1 and PD-L1 confirmed in some solid tumors and lymphoma resulting tumor cells escape the immune system and help to survive and to spread. Inhibitors of PD-1 and PD-L1 have shown lasting responses in several solid and some hematological tumors, while limited studies evaluate checkpoint molecules on PCNSL.<br> <strong>Method</strong>: In this study, we investigated PD-1 and PD-L1 expression by immunostaining on 71 patients with PCNSL and correlation with demographic data, location of the tumor, proliferation rate, cell of origin, and CD8 positive T cell infiltration in tumor microenvironment.&nbsp;<br> <strong>Results</strong>: 16 from71 showed PD-1 expression, while PD-L1 expression were 42/71. No association was determined between PD-1/PD-L1 expression and gender, cell of origin, and proliferation rate, but a highly significant difference was determined between the infiltration of CD8 positive T cells in two groups of PD-1/PD-L1 positive and negative.&nbsp;<br> <strong>Conclusion</strong>: This study revealed expression of check point molecules in remarkable number of PCNSL which may open new therapeutic recommendations in this aggressive lymphoma type.</div> Primary large B-cell lymphoma, CNS, Immune checkpoint, Programmed death-1 (PD-1), Programmed death-1 ligand (PD-L1), Central nervous system 491 498 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2542-1&slc_lang=en&sid=1 Ahmad Monabati monabati.am@gmail.com 13700319475328460029064 13700319475328460029064 No Department of Pathology, Hematology Research Center, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran. Pardis Nematollahi pardis.nematolahy@med.mui.ac.ir 13700319475328460029065 13700319475328460029065 Yes Department of Pathology, Cancer Prevention Research Center, Isfahan University of Medical Science, Isfahan, Iran. Amirreza Dehghanian adehghan@sums.ac.ir 13700319475328460029066 13700319475328460029066 No Department of Pathology, Molecular Pathology and Cytogenetics Division, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran. Akbar Safaei safaeia@sums.ac.ir 13700319475328460029067 13700319475328460029067 No Department of Pathology, Hematology Research Center, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran. Alireza Sadeghipour sadeghipour.alireza@gmail.com 13700319475328460029068 13700319475328460029068 No Department of Pathology, Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran. Sajjadeh Movahedinia sajjadehmovahedinia@gmail.com 13700319475328460029069 13700319475328460029069 No Department of Pathology, Faculty of Medicine, Kerman University of Medical Science, Kerman, Iran. Maral Mokhtari maral_mokhtari@yahoo.com 13700319475328460029070 13700319475328460029070 No Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.