NPC is a malignancy arising from the epithelium of the nasopharynx. Environmental factors, genetic background, and EBV infection are reported to be involved in the etiology of the disease. Radiotherapy or chemo-radiotherapy are the major treatment regimens for NPC. However, some patients develop relapse or metastasis disease. Therefore, finding new prognostic factors for NPC patients is an urgent need. In the present study, we investigated the prognostic value of CD47 and SIRI in a retrospective cohort of 183 NPC patients. The results showed that patients with low CD47 expression and low SIRI level had longer PFS and OS, and CD47/SIRI statue was an independent prognostic factor for NPC patients’ prognosis.
The development and progression of tumors occur in concert with alterations in the surrounding environment. Previous research has shown that local and systemic immune inflammation statue are interconnected and significantly associated with disease progression and patients’ prognosis. The secretion of various cytokines, and chemokines can affect the tumor microenvironment (TME). Several blood-based inflammation biomarkers have been established as effective prognostic biomarker in NPC, including NLR and PLR, etc. SIRI is a newly established biomarker, which reflected the change of neutrophil, monocyte and lymphocyte associated with systemic inflammation statue. It has been studied as a prognostic biomarker in NPC patients[20, 21]. In the present study, we also found that SIRI is a prognostic factor for PFS, which is in accordance with previous reports. It indicated that SIRI could be an effective systemic inflammation biomarker for prognosis prediction.
CD47 is an importance biomarker presenting local immune statue in the TME. It is a transmembrane protein which plays an important role in mediating cell proliferation, migration, phagocytosis, apoptosis, immune homeostasis and other immune reactions. CD47 binds to signal regulatory proteins (SIRPs) with high affinity. The binding of CD47 and SIRPs sends a “don’t eat me” signal to the macrophages, and inhibits phagocytosis of tumor cells by macrophages, leading to immune suppression. Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. Therefore, research of CD47-SIRPα immune checkpoint in tumor immunotherapy has become more and more popular in recent years. The prognostic role of CD47 expression has been shown in several cancers. A retrospective study of colorectal cancer showed that high expression of CD47 correlated with distant metastasis and shorter PFS. In advanced non-small cell lung cancer, high expression of CD47 (with a cut-off of TPS≥50%) predicted shorter PFS and OS.
The evidence of prognostic role of CD47 expression in NPC patients is limited. In a previous study, 66 NPC patients were retrospectively investigated, results showed that high expression of CD47 (with a cut-off of TPS≥10%) was an independent prognostic factor for PFS (HR=5.452, p=0.016). In the present study, we found in a larger cohort that CD47 expression is an independent prognostic factor for NPC patients’ prognosis, which was in consistent with the previous findings. Moreover, we combined the biomarker of local immune statue, CD47, and the biomarker of systemic immune statue, SIRI, and found that patients with low CD47 expression and low SIRI level had better PFS and OS. It indicated that both a local and systemic immunocompetent statue are needed to avoid tumor immune escape and disease progression. CD47 is a promising new immune checkpoint in tumor immunotherapy, and multiple clinical trials involving CD47-SIRPα blocking agents are ongoing for leukemia, lymphoma, and solid tumors. Further studies are needed to evaluate prognostic and therapeutical significance of CD47 in cancers.
Obviously, our study has several limitations. Firstly, it is a retrospective study with comparatively small sample size, which may bring selection bias. Secondly, the cut-off value of CD47 TPS in our study was different from previous study. Since the data from large sample size research is lacking, the optimal cut-off value still needs further investigation. Thirdly, some other clinicopathological factors which may affect the prognosis of patients were not included, such as EBV-DNA, LDH. It may bring bias to the results.
In summary, our study indicated that combination of CD47 expression and SIRI may be a promising prognostic biomarker. It is a convenient and easy-to-get biomarker that may help patient stratification. However, the underlying mechanism of the mutual effecting of local and systemic immune statue in cancer immune escaping and disease progression still needs further investigation.