Different clinical significance of novel B7 family checkpoints VISTA and HHLA2 in human lung adenocarcinoma.

Background: VISTA and HHLA2 are two recently identified members of the B7 homologue family of immune-regulatory molecules. But the expression patterns and clinical significance of VISTA and HHLA2 in lung adenocarcinoma (LUAD) remain largely unknown. Methods: Immunohistochemistry was performed to examine the expression of VISTA, HHLA2, PD-L1 and CD8+ tumor-infiltrating lymphocytes in 74 cases of LUAD. The expression of VISTA, HHLA2, PD-L1, CD68 and CD8 proteins was detected by multiplex immunofluorescence staining in the LUAD tissues. Results: High expression of VISTA and HHLA2 was observed in LUAD compared with noncancerous tissues. High VISTA expression in immune cells predicted a high mortality rate and worse survival. Conclusion: VISTA and HHLA2 are potential immunotherapeutic targets that possess different prognostic significance in LUAD.

[1]  Yunyun Liu,et al.  HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer , 2021, Cancer cell international.

[2]  Y. Hong,et al.  Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby , 2021, Frontiers in Oncology.

[3]  Chen Zhao,et al.  Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy , 2021, Cancers.

[4]  Jifeng Feng,et al.  B7-H4 and HHLA2, members of B7 family, are aberrantly expressed in EGFR mutated lung adenocarcinoma. , 2020, Pathology, research and practice.

[5]  W. Guo,et al.  High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict worse survival in human lung adenocarcinoma , 2020, Journal of Cancer.

[6]  A. Turtoi,et al.  High Stromal TGFBI in Lung Cancer and Intratumoral CD8-Positive T Cells were Associated with Poor Prognosis and Therapeutic Resistance to Immune Checkpoint Inhibitors , 2019, Annals of Surgical Oncology.

[7]  C. V. van Eijck,et al.  HHLA2 is expressed in pancreatic and ampullary cancers and increased expression is associated with better post-surgical prognosis , 2020, British Journal of Cancer.

[8]  S. Rieder,et al.  B7-H7 (HHLA2) inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling , 2020, Cellular & molecular immunology.

[9]  Ran-yi Liu,et al.  HHLA2 and PD-L1 co-expression predicts poor prognosis in patients with clear cell renal cell carcinoma , 2020, Journal for ImmunoTherapy of Cancer.

[10]  A. Yamniuk,et al.  VISTA is an acidic pH-selective ligand for PSGL-1 , 2019, Nature.

[11]  R. Noelle,et al.  VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity. , 2019, Seminars in immunology.

[12]  Xianda Zhao,et al.  Targeting Immune Checkpoints in Lung Cancer: Current Landscape and Future Prospects , 2019, Clinical Drug Investigation.

[13]  W. Tsai,et al.  HHLA2 is a novel immune checkpoint protein in pancreatic ductal adenocarcinoma and predicts post-surgical survival. , 2019, Cancer letters.

[14]  Jun Yu Li,et al.  VSIG‐3 as a ligand of VISTA inhibits human T‐cell function , 2018, Immunology.

[15]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[16]  Colin C. Pritchard,et al.  Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease , 2018, Journal of Immunotherapy for Cancer.

[17]  J. Fisher,et al.  VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival , 2018, Cancer Immunology, Immunotherapy.

[18]  Li-xu Yan,et al.  VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma , 2018, BMC Cancer.

[19]  S. Natsugoe,et al.  The association of human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) expression with gastric cancer prognosis , 2018, Oncotarget.

[20]  J. Wilmott,et al.  Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients , 2017, Modern Pathology.

[21]  T. Fujii,et al.  Prognostic value of programmed death‐ligand 1 expression in patients with stage III colorectal cancer , 2017, Cancer science.

[22]  I. Wistuba,et al.  VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer , 2017, Nature Medicine.

[23]  E. Richardsen,et al.  Assessing PDL‐1 and PD‐1 in Non–Small Cell Lung Cancer: A Novel Immunoscore Approach , 2017, Clinical lung cancer.

[24]  Lei Wu,et al.  Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma , 2017, Cancer Immunology, Immunotherapy.

[25]  Y. Maehara,et al.  Clinical Significance of PD‐L1 Protein Expression in Surgically Resected Primary Lung Adenocarcinoma , 2016, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[26]  X. Zang,et al.  HHLA2, a member of the B7 family, is expressed in human osteosarcoma and is associated with metastases and worse survival , 2016, Scientific Reports.

[27]  W. Suh,et al.  The CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy , 2014, Immune network.

[28]  H. Kohrt,et al.  Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients , 2014, Nature.

[29]  R. Emerson,et al.  PD-1 blockade induces responses by inhibiting adaptive immune resistance , 2014, Nature.

[30]  J. Taube,et al.  B7-H5 costimulates human T cells via CD28H , 2013, Nature Communications.

[31]  X. Zang,et al.  HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function , 2013, Proceedings of the National Academy of Sciences.

[32]  Zonghuan Li,et al.  Caveolin-1 Expression Level in Cancer Associated Fibroblasts Predicts Outcome in Gastric Cancer , 2013, PloS one.

[33]  Angela N. Brooks,et al.  Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing , 2012, Cell.

[34]  A. Jemal,et al.  Cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[35]  Frank C. Detterbeck,et al.  The Eighth Edition Lung Cancer Stage Classification , 2017, Chest.