CD155 expression in human breast cancer: Clinical significance and relevance to natural killer cell infiltration

Triki, H.; Charfi, Slim; Bouzidi, Lobna; Kridis, Wala Ben; Daoud, J.; Chaabane, Kais; Sellami‐Boudawara, Tahya; Rebai, Ahmed; Cherif, Boutheina

doi:10.1016/j.lfs.2019.116543

Cited by 58 publications

(50 citation statements)

References 46 publications

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“…31 In two recently published studies, the authors analyzed the PVR protein expression by immunohistochemistry in large cohorts of breast cancer patients. In both studies, high PVR expression was associated with poor patients' outcome 41,42 supporting our findings. Moreover, these observations are in line with the correlation between PVR mRNA and protein levels that we found in our patient cohort.…”

Section: Discussionsupporting

confidence: 90%

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

et al. 2019

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Immune checkpoints are intensively investigated as targets in cancer therapy. T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) and its ligand poliovirus receptor (PVR) are recently emerging as novel promising targets in immunotherapy. Here, we show that high expression of PVR represents an independent prognostic marker being associated with poor outcome for breast cancer patients. Furthermore, PVR mRNA, as well as protein expression, is associated with more aggressive breast cancer subtypes such as HER2 positive and triple-negative breast cancer. In vitro, blocking TIGIT or PVR resulted in enhanced immune cell-mediated lysis of breast cancer cell lines SKBR-3, MDA-MB-231, MDA-MB-468, and BT549 and additionally increased the cytotoxic effects of a bispecific T cell engager BiTE® antibody construct targeting EGFR. Taken together, our data identify the immune checkpoint factor PVR as a novel prognostic marker in breast cancer and indicate that blocking the TIGIT-PVR axis might represent a novel therapeutic option for the treatment of breast cancer patients.

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Section: Discussionsupporting

confidence: 90%

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

et al. 2019

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“…The prognostic effect of CD155 expression on BC was confirmed in another two publications [25,26]. The two articles presented a significant association between CD155 expression with NK [25] and cytotoxic and macrophage-TILs [26]; however, we not only observed a significant relationship with TILs but also a significant relationship with PD-1 + TILs (dysfunctional TILs). Therefore, we concluded the exhausted TILs, but not the functional TILs related with CD155.…”

Section: Discussionsupporting

confidence: 71%

“…Intratumoral treatment of the recombinant nonpathogenic polio-rhinovirus chimera to patients with recurrent glioblastoma prolonged the survival length, comparing with the historical controls [24]. The prognostic effect of CD155 expression on BC was confirmed in another two publications [25,26]. The two articles presented a significant association between CD155 expression with NK [25] and cytotoxic and macrophage-TILs [26]; however, we not only observed a significant relationship with TILs but also a significant relationship with PD-1 + TILs (dysfunctional TILs).…”

Section: Discussionmentioning

confidence: 83%

Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

Zhou

Song

et al. 2020

Journal of Immunology Research

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Purpose. The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer. Methods. 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association. Results. 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively (p<0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1+ lymphocytes was significantly higher (52/HPF vs. 25/HPF, p<0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively (p<0.05). CD155 overexpression was associated with an increased relapse (HR=13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR=5.47,1.42,20.99). Conclusions. Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer.

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“… 51 2016 2006 – 2008 Breast Cancer Invasive ductal carcinoma 278 278:0 Mean NR (28–75) NKp46 (ab199128) Quantified in Str based on density: • 0 (absent) • 3 (dense) NR 0.54 (0.39 – 0.74, p = 0.001) Improved, OS ( p = 0.018) Improved DFS, ( p < 0.001) Triki et al. 52 2019 NR Breast Cancer NR 158 158:0 118 patients>40 40 patients <40 CD56 (1BC) Quantified as: • low (negative or weak infiltration) • high (moderate or strong infiltration) NR 0.17 (0.039 – 0.73, p = 0.017) Improved, OS ER+: p = 0.007 PR+: p = 0.018 HER+ p = 0.287 Vgenopoulou et al. 53 2003 NR Breast Cancer Invasive ductal carcinoma 64 64:0 NR CD57 (TB01) Quantified based on staining intensity as: • Weak-moderate • Strong NR NR No change, DFS (NR) Wang et al.…”

Section: Methodsmentioning

confidence: 99%

NK cell infiltration is associated with improved overall survival in solid cancers: A systematic review and meta-analysis

Nersesian

Schwartz

Grantham

et al. 2021

Translational Oncology

121

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Highlights NK cell infiltration to solid tumors independently predicts improved OS. We reviewed 53 studies and meta-analyzed hazard ratios from 30. Meta-analysis revealed that NK cell infiltration predicts decreased risk of death. NK prognostic value is related to identifying marker and subtumor location. NK cell infiltration may be associated with tumor stage and grade.

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CD155 expression in human breast cancer: Clinical significance and relevance to natural killer cell infiltration

Cited by 58 publications

References 46 publications

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

NK cell infiltration is associated with improved overall survival in solid cancers: A systematic review and meta-analysis

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