Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T‐cell leukemia/lymphoma

Abstract

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces "don't eat me signal", leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL. K E Y W O R D S CD47, signal regulatory protein α (SIRPα), adult T-cell leukemia/lymphoma(ATLL) 1 | INTRODUCTION Adult T-cell leukemia-lymphoma (ATLL) is a mature T-cell neoplasm induced by human T-lymphotropic virus type 1. 1 ATLL is classified into four categories: acute, lymphomatous, chronic, and smoldering types based on the clinical findings. 2 Acute and lymphomatous types are regarded as an aggressive type with poor prognosis compared with chronic and smoldering types. 2 It is difficult for patients with aggressive ATLL to prolong survival by conventional chemotherapy alone. 3 One of the recent therapies for ATLL is molecular target-based

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

“…Previous studies have reported that SIRPα + macrophage infiltrates were correlated with shorter overall survival and progression-free survival in other malignancies, such as diffuse large B-cell lymphoma 32 and melanoma and renal cell carcinoma 39 . However, other reports have also shown a positive correlation between SIRPα expression and good prognosis 33 . In our immunohistochemical studies, it was suggested that SIRPα enabled tumor cells to evade phagocytosis, leading to promoted tumor growth and progression, similar to PD-L1 expression in GCTB patients.…”

“…Moreover, SIRPα + , CD8 + , and FOXP3 + cells were counted per high power field in five dependent fields for each case. This process was based on previous studies, with modifications 32 , 33 , 49 – 51 . Statistically, the median numbers of SIRPα + , CD8 + , and FOXP3 + cells were determined as the cut-off points.…”

“…Cluster of differentiation 47 (CD47) and signal-regulatory protein alpha (SIRPα) are “don’t eat me” signals, and they promote escape from phagocytosis in malignant tumors 31 – 33 , enabling lymphoma cells to evade phagocytosis and thereby promoting tumor growth 32 . Dancsok et al investigated SIRPα expression in various bone and soft tissue sarcomas and reported that some sarcomas showed shorter progression-free survival with PD-L1 expression 31 .…”

Expression of telomerase reverse transcriptase in peripheral T‐cell lymphoma

“…PTCL-NOS and ATLL cases were included in our previous studies. [16][17][18][19][20][21] All cases were reviewed by experienced hematopathologists (O. K., M. H.) according to the World Health Organization classification. 22 Clinical information was collected by reviewing the patients' medical charts.…”

Tumor microenvironment of adult T-cell leukemia/lymphoma

“… 33 On the other hand, stromal expression of SIRPα was detected as a good prognostic factor. 38 Although the precise mechanism remains unclear, those with SIRPα-expressing stromal cells had significantly higher expression of MHC class I and/or MHC class II, and also had PD-L1 expressing stromal cells, suggesting that SIRPα-expressing stromal cells are associated with activated anti-tumor immunity. 38 …”