Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A new era in cancer active immunotherapy

Constantinidou, Anastasia; Alifieris, Constantinos; Trafalis, Dimitrios T.

doi:10.1016/j.pharmthera.2018.09.008

Cited by 279 publications

(251 citation statements)

References 203 publications

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“…TMB is defined as the total number of mutations per coding area of a tumor genome, and the number of mutations range from a few to thousands 4 . As shown in a recent review by Galuppini et al, 17 tumors due to powerful carcinogenic and mutagenic agents or caused by germline mutations in genes that encode proteins involved in DNA repair pathways tend to have higher TMB.…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of tumor mutation burden in hepatocellular carcinoma after radical hepatectomy

Cai

Zhang

Cui

et al. 2020

Journal of Surgical Oncology

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Background and Aim This study aimed to assess the potential relationship between tumor mutation burden (TMB) and the recurrence risk of hepatocellular cancer (HCC) after curative resection and tried to develop a reliable TMB based nomogram. Methods This retrospective study was conducted in 128 patients (40 patients suffered from a recurrence of HCC) who had received radical hepatectomy by the same surgical team. A nomogram model was constructed using the R and EmpowerStats software. Results TMB was not associated with maximum tumor size and the presence of microvascular invasion (MVI). In the whole population or subgroups, the recurrence‐free survival (RFS) rate was significantly lower in the TMB high group. In multivariate analysis, TMB (hazard ratio [HR], 10.12; 95% confidence interval [CI], 5.03‐20.31; P < .001), large tumor diameter (HR, 2.91; 95% CI, 1.51‐5.63; P = .001), presence of MVI (HR, 1.93; 95% CI, 1.03‐3.65; P = .042) were independent predictors of RFS. The predictive power of the nomogram integrating TMB, tumor size and MVI was higher than model only incorporating tumor size and MVI. Conclusion This study demonstrated for the first time that higher TMB was associated with poor prognosis in patients with HCC who had received curative resection, and a TMB based nomogram model had a well predictive performance for RFS in this population.

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Section: Discussionmentioning

confidence: 99%

Prognostic role of tumor mutation burden in hepatocellular carcinoma after radical hepatectomy

Cai

Zhang

Cui

et al. 2020

Journal of Surgical Oncology

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“…PD‐L1 is expressed in resting T cells, B cells, dendritic cells, and various tumor cells. When the PD‐1 molecule binds to the PD‐L1 receptor ligand, this complex inhibits cytotoxic T cells, thus leading to apoptosis and tumor escape . PD‐L1 overexpression in renal cell carcinoma, esophageal cancer, and melanoma is associated with worse prognosis and outcomes .…”

Section: Discussionmentioning

confidence: 99%

Prognostic markers in salivary gland cancer and their impact on survival

et al. 2019

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Background The role of molecular markers in salivary gland carcinoma (SGC) is not well understood. We evaluated molecular marker expression and their prognostic value. Methods Immunohistochemical analysis of 124 tumor specimens was performed to determine expression of androgen (AR), estrogen (ER), and progesterone (PR) receptors and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 receptor (PD‐L1), and PD‐L1 in tumor‐infiltrating mononuclear cell (TIMC). Survival outcomes (disease‐free survival [DFS] and overall survival [OS]), pT and N classification, margin status, and treatment failure were assessed. Results Most patients (78; 62.9%) had early‐stage SGC. AR positivity and EGFR positivity were detected in 21.0% and 78.6%, respectively, of tumors. AR positivity and PD‐L1 negativity were associated with locally advanced disease. PD‐L1‐negativity was associated with higher recurrence (38.5% vs 0%; P < .001) and worse DFS. OS and DFS were worse in patients with AR+ or HER2+ disease. Conclusions Several molecular markers—AR and HER2 positivity and PD‐L1 negativity—were associated with worse clinical outcomes. Prospective, multi‐institutional trials are needed to determine the prognostic value of these markers.

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“…In tumorigenesis, PD‐1 is expressed in a large proportion of tumour‐infiltrating lymphocytes in several tumour histologies, including melanoma, non‐small cell lung cancer and carcinoma of the head and neck. The degree of expression of its ligand, PD‐L1, on tumour cells, as an indicator of PD‐1/PD‐L1 activation and thus evasion from immune surveillance, is found to be a biomarker that may indicate potential response to PD‐1 or PD‐L1 checkpoint inhibitors . In the current study, Cubillos‐Zapata et al .…”

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confidence: 55%

“…At the same time, PD‐1/PD‐L1 activation may become an escape mechanism from the body's physiological immune surveillance on tumours or infections. Activation of the PD‐1/PD‐L1 axis in the tumour microenvironment is believed to be a major contributor to the evasion of immune surveillance against cancer within the tumour microenvironment, and the advent of PD‐1/PD‐L1 checkpoint inhibitors has brought on a rapidly evolving era of immunotherapy in cancer treatment . In tumorigenesis, PD‐1 is expressed in a large proportion of tumour‐infiltrating lymphocytes in several tumour histologies, including melanoma, non‐small cell lung cancer and carcinoma of the head and neck.…”

mentioning

confidence: 99%

“…The immune network of the human body is tremendously complex. The PD‐L1/PD‐1 pathway has come into the limelight partly due to the success story seen in cancer immunotherapy specifically targeting this pathway and the role of PD‐L1 expression in tumour cells as a biomarker predicting treatment response, yet despite the promising data, it is well recognized that there is still much work to be done before one can draw any clinically meaningful conclusions regarding PD‐L1 expression and treatment response to PD‐1/PD‐L1 checkpoint inhibition . This work by Cubillo‐Zapata et al .…”

mentioning

confidence: 99%

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