Tumor CD73/A2aR adenosine immunosuppressive axis and tumor-infiltrating lymphocytes in diffuse large B-cell lymphoma

correlations with clinicopathological characteristics and clinical outcome

Xianhuo Wang, Tingting Zhang, Zheng Song, Linyu Li, Xuhan Zhang, Jing Liu, Xianming Liu, Lihua Qiu, Zhengzi Qian, Shiyong Zhou, Lixia Feng, Ge Hu, Bin Meng, Qiongli Zhai, Xiubao Ren, Kai Fu, Lanfang Li, Ping Wang, Huilai Zhang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Novel immune checkpoint blockades, including those targeting CD73 and A2aR, are being evaluated in malignancies in clinical trials. Here, we investigated the expression of CD73 and A2aR as well as tumor-infiltrating lymphocytes (TILs), and analyzed their correlations with clinicopathological characteristics and survival in diffuse large B-cell lymphoma (DLBCL). We found that CD73 expression on tumor cells, rather than the total protein and gene levels of CD73, was associated with survival. Patients with CD73 + /Pax-5 + (median survival, 57.8 months; 95% CI, 46.4–69.3) experienced significantly poorer outcomes than those with CD73 /Pax-5 + (median survival, 73.5 months; 95% CI, 65.9–81.2). Additionally, A2aR expression on both total TILs and CD8 + TILs was correlated with survival. Patients with A2aR + TILs (median survival, 53.3 months; 95% CI, 40.6–66.0) had a significantly shorter survival time than patients with A2aR TILs (median survival, 74.5 months; 95% CI, 67.5–81.5). Spearman's rank test showed that CD73 expression on tumor cells was positively correlated with A2aR expression on TILs (R = 0.395, p = 0.001). We further found that patients could be more precisely stratified through the combination of CD73 tumor cell expression and A2aR TILs expression, and patients with CD73 + /Pax-5 + and A2aR + TILs experienced the worst outcome. We also revealed that patients with CD73 + /Pax-5 + and low CD8 + TILs or low absolute lymphocyte counts had unfavorable outcomes. Overall, our findings uncovered that patients with CD73 + on tumor cells as well as A2aR + on TILs or low CD8 + TILs exhibited inferior survival, supporting potential combination strategies using CD73/A2aR immunosuppressive blockades as treatment options for DLBCL patients.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StatePublished - Jan 1 2019

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Tumor-Infiltrating Lymphocytes
Lymphoma, Large B-Cell, Diffuse
Immunosuppressive Agents
Adenosine
Survival
Neoplasms
Lymphocyte Count

Keywords

  • A2aR
  • CD73
  • DLBCL
  • immune checkpoint
  • tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tumor CD73/A2aR adenosine immunosuppressive axis and tumor-infiltrating lymphocytes in diffuse large B-cell lymphoma : correlations with clinicopathological characteristics and clinical outcome. / Wang, Xianhuo; Zhang, Tingting; Song, Zheng; Li, Linyu; Zhang, Xuhan; Liu, Jing; Liu, Xianming; Qiu, Lihua; Qian, Zhengzi; Zhou, Shiyong; Feng, Lixia; Hu, Ge; Meng, Bin; Zhai, Qiongli; Ren, Xiubao; Fu, Kai; Li, Lanfang; Wang, Ping; Zhang, Huilai.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Wang, Xianhuo ; Zhang, Tingting ; Song, Zheng ; Li, Linyu ; Zhang, Xuhan ; Liu, Jing ; Liu, Xianming ; Qiu, Lihua ; Qian, Zhengzi ; Zhou, Shiyong ; Feng, Lixia ; Hu, Ge ; Meng, Bin ; Zhai, Qiongli ; Ren, Xiubao ; Fu, Kai ; Li, Lanfang ; Wang, Ping ; Zhang, Huilai. / Tumor CD73/A2aR adenosine immunosuppressive axis and tumor-infiltrating lymphocytes in diffuse large B-cell lymphoma : correlations with clinicopathological characteristics and clinical outcome. In: International Journal of Cancer. 2019.
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abstract = "Novel immune checkpoint blockades, including those targeting CD73 and A2aR, are being evaluated in malignancies in clinical trials. Here, we investigated the expression of CD73 and A2aR as well as tumor-infiltrating lymphocytes (TILs), and analyzed their correlations with clinicopathological characteristics and survival in diffuse large B-cell lymphoma (DLBCL). We found that CD73 expression on tumor cells, rather than the total protein and gene levels of CD73, was associated with survival. Patients with CD73 + /Pax-5 + (median survival, 57.8 months; 95{\%} CI, 46.4–69.3) experienced significantly poorer outcomes than those with CD73 − /Pax-5 + (median survival, 73.5 months; 95{\%} CI, 65.9–81.2). Additionally, A2aR expression on both total TILs and CD8 + TILs was correlated with survival. Patients with A2aR + TILs (median survival, 53.3 months; 95{\%} CI, 40.6–66.0) had a significantly shorter survival time than patients with A2aR − TILs (median survival, 74.5 months; 95{\%} CI, 67.5–81.5). Spearman's rank test showed that CD73 expression on tumor cells was positively correlated with A2aR expression on TILs (R = 0.395, p = 0.001). We further found that patients could be more precisely stratified through the combination of CD73 tumor cell expression and A2aR TILs expression, and patients with CD73 + /Pax-5 + and A2aR + TILs experienced the worst outcome. We also revealed that patients with CD73 + /Pax-5 + and low CD8 + TILs or low absolute lymphocyte counts had unfavorable outcomes. Overall, our findings uncovered that patients with CD73 + on tumor cells as well as A2aR + on TILs or low CD8 + TILs exhibited inferior survival, supporting potential combination strategies using CD73/A2aR immunosuppressive blockades as treatment options for DLBCL patients.",
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AU - Zhang, Tingting

AU - Song, Zheng

AU - Li, Linyu

AU - Zhang, Xuhan

AU - Liu, Jing

AU - Liu, Xianming

AU - Qiu, Lihua

AU - Qian, Zhengzi

AU - Zhou, Shiyong

AU - Feng, Lixia

AU - Hu, Ge

AU - Meng, Bin

AU - Zhai, Qiongli

AU - Ren, Xiubao

AU - Fu, Kai

AU - Li, Lanfang

AU - Wang, Ping

AU - Zhang, Huilai

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AB - Novel immune checkpoint blockades, including those targeting CD73 and A2aR, are being evaluated in malignancies in clinical trials. Here, we investigated the expression of CD73 and A2aR as well as tumor-infiltrating lymphocytes (TILs), and analyzed their correlations with clinicopathological characteristics and survival in diffuse large B-cell lymphoma (DLBCL). We found that CD73 expression on tumor cells, rather than the total protein and gene levels of CD73, was associated with survival. Patients with CD73 + /Pax-5 + (median survival, 57.8 months; 95% CI, 46.4–69.3) experienced significantly poorer outcomes than those with CD73 − /Pax-5 + (median survival, 73.5 months; 95% CI, 65.9–81.2). Additionally, A2aR expression on both total TILs and CD8 + TILs was correlated with survival. Patients with A2aR + TILs (median survival, 53.3 months; 95% CI, 40.6–66.0) had a significantly shorter survival time than patients with A2aR − TILs (median survival, 74.5 months; 95% CI, 67.5–81.5). Spearman's rank test showed that CD73 expression on tumor cells was positively correlated with A2aR expression on TILs (R = 0.395, p = 0.001). We further found that patients could be more precisely stratified through the combination of CD73 tumor cell expression and A2aR TILs expression, and patients with CD73 + /Pax-5 + and A2aR + TILs experienced the worst outcome. We also revealed that patients with CD73 + /Pax-5 + and low CD8 + TILs or low absolute lymphocyte counts had unfavorable outcomes. Overall, our findings uncovered that patients with CD73 + on tumor cells as well as A2aR + on TILs or low CD8 + TILs exhibited inferior survival, supporting potential combination strategies using CD73/A2aR immunosuppressive blockades as treatment options for DLBCL patients.

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