Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study

Lotfinejad, Parisa; Jafarabadi, Mohammad Asghari; Baradaran, Behzad; Kazemi, Tohid; Pashazadeh, Fariba; Shotorbani, Siamak Sandoghchian; Niaragh, Farhad Jadidi; Baghbanzadeh, Amir; Vahed, Nafiseh; Silvestris, Nicola; Baradaran, Behzad

doi:10.3390/diagnostics10090704

Cited by 56 publications

(40 citation statements)

References 36 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies evaluating the prognostic implications of PD-L1 in BC have reported conflicting results. Some reported a positive association between PD-L1 and survival [30][31][32][33][34], whereas others found a negative association [17,25,26] or no association at all [35]. However, these findings must be interpreted with care, because PD-L1 expression may be differentially regulated on tumor or immune cells [29,36,37], and previous studies have highlighted the importance of studying the expression of this molecule in both types of cell [29].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Grandal

Mangiardi-Veltin

Laas

et al. 2021

Cancers

View full text Add to dashboard Cite

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

show abstract

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Grandal

Mangiardi-Veltin

Laas

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Studies evaluating the prognostic implications of PD-L1 in BC have reported conflicting results. Some reported a positive association between PD-L1 and survival [30–34], whereas others found a negative association [17,25,26] or no association at all [35]. However, these findings must be interpreted with care, because PD-L1 expression may be differentially regulated on tumor or immune cells [29,36,37], and previous studies have highlighted the importance of studying the expression of this molecule in both types of cell [29].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression is associated with higher residual cancer burden in triple-negative breast cancers with residual disease after neoadjuvant chemotherapy

Grandal

Mangiardi-Veltin

Laas

et al. 2020

Preprint

View full text Add to dashboard Cite

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well understood. This is an important issue as immune checkpoint inhibitors (ICI) are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression (E1L3N clone, cutoff for positivity: ≥ 1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of surgical specimens of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p=0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with DFS (p=0.38) or OS (p=0.48), but high Ki67 levels after NAC were strongly associated with a poor prognosis (DFS p=0.0014 and OS p=0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

show abstract

“…The overexpression of PD-L1 and CTL-A4 on the tumoral cells shields the tumoral cells from immune responses. Based on recent meta-analyses, there has been a remarkable association between tumor-infiltrating lymphocytes and tumoral PD-L1 expression in triple-negative breast cancer and melanoma ( 55 , 171 ). Despite an increased level of tumor-infiltrating lymphocyte, the PD-L1 up-regulation in tumors represses anti-tumoral immune responses ( 172 , 173 ).…”

Section: The Lessons We Have Learned and The Lessons We Should Learnmentioning

confidence: 99%

From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past

et al. 2021

Self Cite

View full text Add to dashboard Cite

Although melanoma remains the deadliest skin cancer, the current treatment has not resulted in the desired outcomes. Unlike chemotherapy, immunotherapy has provided more tolerable approaches and revolutionized cancer therapy. Although dendritic cell-based vaccines have minor side effects, the undesirable response rates of traditional approaches have posed questions about their clinical translation. The immunosuppressive tumor microenvironment can be the underlying reason for their low response rates. Immune checkpoints and indoleamine 2,3-dioxygenase have been implicated in the induction of immunosuppressive tumor microenvironment. Growing evidence indicates that the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Protein kinase B (PKB) (PI3K/AKT) pathways, as the main oncogenic pathways of melanoma, can upregulate the tumoral immune checkpoints, like programmed death-ligand 1. This study briefly represents the main oncogenic pathways of melanoma and highlights the cross-talk between these oncogenic pathways with indoleamine 2,3-dioxygenase, tumoral immune checkpoints, and myeloid-derived suppressor cells. Moreover, this study sheds light on a novel tumor antigen on melanoma, which has substantial roles in tumoral immune checkpoints expression, indoleamine 2,3-dioxygenase secretion, and stimulating the oncogenic pathways. Finally, this review collects the lessons from the previous unsuccessful trials and integrates their lessons with new approaches in RNA-modified dendritic cell vaccines. Unlike traditional approaches, the advances in single-cell RNA-sequencing techniques and RNA-modified dendritic cell vaccines along with combined therapy of the immune checkpoint inhibitors, indoleamine 2,3-dioxygenase inhibitor, and RNA-modified dendritic cell-based vaccine can overcome these auto-inductive loops and pave the way for developing robust dendritic cell-based vaccines with the most favorable response rate and the least side effects.

show abstract

Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study

Cited by 56 publications

References 36 publications

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

PD-L1 expression is associated with higher residual cancer burden in triple-negative breast cancers with residual disease after neoadjuvant chemotherapy

From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past

Contact Info

Product

Resources

About