Programmed cell death-ligand 2: A neglected but important target in the immune response to cancer?

Solinas, Cinzia; Aiello, Marco Maria; Rozali, Esdy N.; Lambertini, Matteo; Willard-Gallo, Karen; Migliori, Edoardo

doi:10.1016/j.tranon.2020.100811

Cited by 57 publications

(54 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immune checkpoint therapy targeting programmed death ligand-1/2 (PD-L1/2) and programmed cell death protein-1 (PD-1) has emerged as an effective strategy for various cancers, yielding significant improvement in progression-free and overall survival of patients with metastatic cancer [1,2]. Following the great success of therapeutic antibody ipilimumab in advanced melanoma in 2010 [3], several novel monoclonal antibodies (pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab) against these targets have been trialed and approved by the U. S. Food and Drug Administration (FDA) in multiple malignancies [4].…”

Section: Introductionmentioning

confidence: 99%

Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis

et al. 2021

View full text Add to dashboard Cite

Background: Several biomarkers predict the efficacy of immunotherapy, which is essential for selecting patients who would potentially benefit. Discordant status of these biomarkers between primary tumours and paired metastases has been increasingly revealed. We aimed to comprehensively summarize the incidence of this phenomenon. Methods: Databases were searched to identify studies reporting primary-to-metastatic conversion of biomarkers, including programmed death ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), PD-L2, tumour-infiltrating lymphocyte (TIL), tumour mutational burden (TMB), and microsatellite instability (MSI). Findings: 56 studies with 2739 patients were included. The pooled discordance rate of PD-L1 was 22%. The percentage of PD-L1 changed from positive to negative was 41%, whereas that from negative to positive was 16%. The discordance rate for PD-1 and PD-L2 was 26% and 22%, respectively. TIL level was found with a discordance rate of 39%, and changes from high to low (50%) occurred more than that from low to high (16%). No significant difference in TMB was observed between two sites in most studies. MSI status discordance was found in 6% patients, with a percentage of 9% from MSI-high to microsatellite instable (MSS) and 0% from MSS to MSI-high. Interpretation: Our study demonstrates that PD-L1, PD-1, PD-L2, and TIL level had high frequency of discordance, while TMB and MSI status were less likely to change between primary tumours and paired metastases. Therefore, evaluating those frequently altered biomarkers of both primary and metastatic tumours is strongly recommended for precise clinical decision of immune checkpoint treatment. Fund: The National Natural Science Foundation of China (81872152).

show abstract

Section: Introductionmentioning

confidence: 99%

Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Novel pathways involving other inhibitory immunoreceptors, particularly those eliciting T cell suppression, have been discovered and studied to serve as predictive biomarkers in preclinical and clinical models. 1 , 3–8 Among them, lymphocyte-activation gene 3 (LAG3), 9 programmed cell death protein-ligand 2 (PD-L2), 10 B and T lymphocyte attenuator (BTLA), 11 T-cell immunoglobulin and mucin domain 3 (TIM3), 12 , 13 T cell immunoglobulin and ITIM domain (TIGIT), 14 B7-H3, 15 B7-H4, 16 and V-domain Ig suppressor of T-cell activation (VISTA) 17 have been described as emerging targets in the list of immune checkpoints. Moreover, neoantigens represent a promising tool for immunotherapy in oncology.…”

Section: Introductionmentioning

confidence: 99%

VISTA: A Promising Target for Cancer Immunotherapy?

Tagliamento¹,

Agostinetto²,

Borea³

et al. 2021

ITT

Self Cite

View full text Add to dashboard Cite

Agents targeting the B7 family co-inhibitory receptors cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1), or its ligand (PD-L1), have a pivotal role in clinical practice. V-domain Ig suppressor of T-cell activation (VISTA) is a protein highly conserved between species, with a similar amino acid sequence to the B7 family members, characterized by a particularly structural homology to PD-1. It has been counted as an emerging target within the list of novel targetable immune checkpoints in oncology. Physiologically, VISTA exerts a regulatory function on the immune system at several levels, particularly by modulating T cells activation. Its altered activity plays a role in many autoimmune diseases, and its expression has been found to be prognostically implicated in different cancer types in preclinical models. We hereby present the main evidence on the value of VISTA as an immune checkpoint in solid and hematological malignancies. We also review its value as a potential target for cancer immunotherapy, by reporting the results of Phase I and II clinical trials assessing the use of drugs targeting VISTA. The complexity of its pathway, along with some unclear biological aspects concerning its molecular interactions, currently represent a limit to the applicability of VISTA as an effective biomarker for immunotherapy in oncology. A deeper characterization of this immune checkpoint may help defining its value within immune signatures of solid and hematological malignancies, and to design future therapeutic strategies.

show abstract

“…PD‐L2 expression is less abundant than PD‐L1 expression 3 . While the clinical relevance of PD‐L1 has been widely investigated, PD‐L2 has received less attention in cancer research 11 . Nevertheless, PD‐L2 expression has been demonstrated on both malignant and/or non‐malignant cells of the tumor microenvironment in lymphoid malignancies, including HL and DLBCL 6,12‐14 .…”

Section: Introductionmentioning

confidence: 99%

Soluble programmed cell death protein 1 (sPD‐1) and the soluble programmed cell death ligands 1 and 2 (sPD‐L1 and sPD‐L2) in lymphoid malignancies

Mortensen

Monrad

Enemark

et al. 2021

European J of Haematology

View full text Add to dashboard Cite

Background The programmed cell death protein 1 (PD‐1) and its ligand 1 and 2 (PD‐L1/PD‐L2) regulate the immune system, and the checkpoint pathway can be exploited by malignant cells to evade anti‐tumor immune response. Soluble forms (sPD‐1/sPD‐L1/sPD‐L2) exist in the peripheral blood, but their biological and clinical significance is unclear. Method Time‐resolved immunofluorometric assay (TRIFMA) and enzyme‐linked immunosorbent assay (ELISA) were used to measure sPD‐1, sPD‐L1, and sPD‐L2 levels in serum from 131 lymphoma patients and 22 healthy individuals. Results Patients had higher sPD‐1 and sPD‐L2 levels than healthy individuals. In diffuse large B‐cell lymphoma, patients with high International Prognostic Index score had higher sPD‐1 levels and sPD‐L2 levels correlated with subtype according to cell of origin. Compared to other lymphoma types, follicular lymphoma displayed higher sPD‐1 and lower sPD‐L1 levels along with lower ligand/receptor ratios. Conclusion This is the first study to simultaneously characterize pretherapeutic sPD‐1, sPD‐L1, and sPD‐L2 in a variety of lymphoma subtypes. The relation between higher sPD‐1 levels and adverse prognostic factors suggests a possible biological role and potential clinical usefulness of sPD‐1. Moreover, the reverse expression pattern in follicular lymphoma and T‐cell lymphoma/leukemia may reflect biological information relevant for immunotherapy targeting the PD‐1 pathway.

show abstract

Programmed cell death-ligand 2: A neglected but important target in the immune response to cancer?

Cited by 57 publications

References 99 publications

Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis

Discordance of immunotherapy response predictive biomarkers between primary lesions and paired metastases in tumours: A systematic review and meta-analysis

VISTA: A Promising Target for Cancer Immunotherapy?

Soluble programmed cell death protein 1 (sPD‐1) and the soluble programmed cell death ligands 1 and 2 (sPD‐L1 and sPD‐L2) in lymphoid malignancies

Contact Info

Product

Resources

About