Exploring PD-1/PD-L1 Expression in Mantle Cell Lymphoma and its Significance as an Immune Check Point Inhibitor

Findings from a recent publication suggest that neither Programmed Death 1 (PD-1) nor its ligands represent pertinent targets for mantle cell lymphoma (MCL) treatment, and that age may impact the efficiency of immune checkpoint inhibitors and could be correlated with the augmented occurrence of MCL with age (BMC Cancer. 2022; 22(1):848. doi: 10.1186/s12885-022-09803-x).

Fereshteh Ameli, MD, Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran and colleagues conducted a retrospective study in an attempt to ascertain PD-1/PD-L1 expression in MCL specimens and its significance as an immune check point inhibitor.

This study was conducted on the formalin-fixed paraffin-embedded blocks of 79 confirmed MCL patients based on immunohistochemistry (IHC). The IHC method was used to stain patient samples for PD1 and PDL1. Positive PD-1/PD-L1 expression was defined as moderate to strong or membranous or memberanous/cytoplasmic staining in at least 5% of tumor and/or 20% of associated immune cells. Tumor aggressiveness was established based on Ki67 and variant.

Results revealed that the average age of patients was 60.08 ± 10.78 years old. Majority of the patients were male. The prevalence of aggressive tumor was 25%. Positive PD1 and PDL1 expression were identified in 12 (15.0%) and 3 (3.8%) of tumor cells, respectively. PD1 and PDL1 were positive in zero (0%) and 7 (8.9%) of background cells, respectively. There was no considerable difference in terms of study parameters between positive and negative groups for both PD1 and PDL1 proteins. PD1 tumor cell percentage was negatively correlated with age (r =-0.254, p= 0.046).

Dr Ameli and colleagues wrote, “The findings of the present study indicated a relatively low immunohistochemical expression for PD1 and PDL1 markers in tumoral and background cells in patients with mantle cell lymphoma,” adding, “Therefore, PD1 or PDL1 inhibitors do not seem to be suitable treatment options for immunotherapy in most patients with mantle cell lymphoma.” Age may have a negative effect on the effectiveness of checkpoint inhibitor therapy. “This finding may also explain the increase in the risk of cancer with age due to immune senescence which should be further investigated,” wrote the authors, concluding, “Finally, understanding the interaction between malignant cells, and immune-accompanying cells in tumor microenvironment is mandatory for the purpose of choosing the best treatment option.”