Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy

Nagato, Toshihiro; Komatsuda, Hiroki; Hayashi, Ryusuke; Takahara, Miki; Kishibe, Kan; Yasuda, Shunsuke; Yajima, Yuki; Kosaka, Akemi; Ohkuri, Takayuki; Oikawa, Kensuke; Harabuchi, Shohei; Kono, Michihisa; Yamaki, Hidekiyo; Wakisaka, Risa; Hirata-Nozaki, Yui; Ohara, Kenichi; Kumai, Takumi; Katada, Akihiro; Hayashi, Tatsuya; Harabuchi, Yasuaki; Kobayashi, Hiroya

doi:10.1007/s00262-023-03394-7

Cited by 2 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to our abovementioned finding of an association between EBER and CD70 expression in NPC (Table 2), it has been shown that EBV infection might promote the induction of CD70 expression on tumor cells in some malignancies 24 . In addition, previous studies have reported that the EBV oncoprotein LMP1 can upregulate CD70 expression in epithelial and hematological cells 13,15,25 . To determine whether the expression of CD70 in tumor cells of NPC is associated with EBV infection and LMP1 expression, we examined the expression of CD70 using two NPC cell lines, C666‐1 and TW03.…”

Section: Resultssupporting

confidence: 70%

“…Other studies have reported the detection of sCD27 in the serum of patients with some CD70‐positive tumors, reflecting the interaction between CD70 and CD27 in the tumor microenvironment 9–13 . Therefore, we measured the concentration of sCD27 in the serum of 29 of 41 NPC patients and 23 healthy volunteers.…”

Section: Resultsmentioning

confidence: 97%

“…Serial sections were used for CD70 and CD27 or CD70 and LMP1 staining. A case was considered CD70 positive if >10% of the tumor cells were positive for CD70, as described previously by other researchers and us 11,13 . In addition, the degree of CD70 staining intensity was classified as follows: no, weak, moderate, and strong.…”

Section: Methodsmentioning

confidence: 99%

“…In the analysis to evaluate the relevance of CD70 expression to survival, moderate and strong staining was defined as high CD70 expression, and no or low staining was defined as low CD70 expression. When >5% of tumor‐infiltrating mononuclear immune cells were positive for CD27, the specimen was defined as CD27 positive 13 . The presence of EBV‐encoded small RNA (EBER) in FFPE tissue sections was detected using in situ hybridization, as described previously 20,21 …”

Section: Methodsmentioning

confidence: 99%

“…Another important aspect of the CD70/CD27 interaction is that soluble CD27 (sCD27) is cleaved from the extracellular domain of CD27 upon ligation of CD27 to CD70. 5,6 Indeed, high levels of sCD27 have been found in the serum of patients with some CD70expressing tumors, [9][10][11][12][13] suggesting that measurement of serum sCD27 levels may be useful for predicting the interaction between CD70-positive tumor cells and CD27-positive TILs in order to determine the indication of CD70/CD27-targeted immunotherapies.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Soluble CD27 as a predictive biomarker for intra‐tumoral CD70/CD27 interaction in nasopharyngeal carcinoma

Nagato,

Komatsuda,

Hayashi

et al. 2024

Cancer Science

Self Cite

View full text Add to dashboard Cite

In CD70‐expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)‐related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27‐positive lymphocytes infiltrate around tumor cells. NPC patients with CD27‐positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27‐positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70‐positive NPC with CD27‐positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27‐targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

show abstract

Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%