High Expression of CXCR4, Instead of PD-L1, Is Correlated with Poor Clinical Response to R-CHOP Therapy in Diffuse Large B-cell Lymphoma Patients

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin Lymphoma worldwide. Rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone (R-CHOP) are the current standard therapy. About 10% cases of DLBCL were refractory to these immunochemotherapy and may have poor prognosis. Latest studies showed that C-X-C chemokine receptor type 4 (CXCR4) and Programmed Death Ligand 1 (PD-L1) were involved in DLBCL biology and correlated with patients’ poor survival. This study aimed to investigate the expression of CXCR4 and PD-L1 with clinical characteristics and its response to R-CHOP in DLBCL and their potential benefit as future predictive biomarkers.
 Methods: Thirty four cases of newly diagnosed DLBCL were selected from Hasan Sadikin General Hospital, Bandung, Indonesia, during 2015-2018. Treatment outcome was retrieved from patients’ medical records. The expression of CXCR4 and PD-L1 in patients’ tumor tissues were detected using immunohistochemistry.
 Results: Five of 34 cases (14.70%) showed poor clinical response to R-CHOP. High CXCR4 expression was detected in 11 of 34 cases (32.35%), it was significantly correlated with clinical stage (p = 0.0003) and poor clinical response (p = 0.029). High PD-L1 expression was detected in 10 of 34 cases (29.41%) and was significantly correlated with patients’ gender (p = 0.022) but was not correlated with poor clinical response (p = 0.138).
 Conclusions: CXCR4 in DLBCL increased probability of poor clinical response to R-CHOP, but not PD-L1 expression. This finding provides the ground for further research which relates to CXCR4 as a future predictive biomarker for this challenging malignancy.