Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

Mansfield, Aaron S.; Aubry, MC; Moser, Justin; Harrington, Susan M.; Dronca, Roxana S.; Park, S. S.; Dong, Haidong

doi:10.1093/annonc/mdw289

Cited by 291 publications

(237 citation statements)

References 30 publications

Supporting

Mentioning

219

Contrasting

Unclassified

Order By: Relevance

“…A similar spatial and temporal heterogeneity has been described in other malignancies such as clear cell renal carcinoma, melanoma, and lung cancer. [38][39][40][41] This finding has implications for designing clinical trials and for retesting of metastatic neoplasms, which may be more or less accessible than their primary counterparts. This is particularly relevant for cSCC as the histologic material of the primary site may not be easily available for testing in many metastatic cases.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

et al. 2017

View full text Add to dashboard Cite

Programmed cell death (PD-1) and its ligand (PD-L1) inhibitors have shown clinical response in many tumours. PD-L1 data are limited in head and neck cutaneous squamous cell carcinoma (HNcSCC) and no clinical trials of PD-1/PD-L1 inhibitors are published. We performed PD-L1 immunohistochemistry on 74 cases of high risk HNcSCC with 38 matched metastases and evaluated clinicopathological associations, prognostic significance and heterogeneity in matched metastases. We observed PD-L1 expression in >5% of primary tumour cells in 29 cases (39.2%), primary tumour infiltrating lymphocytes (TILs) in 40 cases (70.2%), metastatic tumour cells in 15 cases (39.5%), and metastatic TILs in 18 cases (47.4%). PD-L1 expression in >5% of primary tumour cells was associated with an inflammatory phenotype (p = 0.04), and in primary TILs with clear margins (p = 0.05). PD-L1 expression in >5% of primary tumour cells (p = 0.01), primary TILs (p = 0.001), and metastatic TILs (p = 0.02) was associated with improved disease free survival. PD-L1 expression in >5% of tumour cells was heterogeneous between primary and metastatic tumours in 13 cases (34.2%). PD-L1 expression is common in HNcSCC supporting the rationale for a clinical trial of PD-1/ PD-L1 inhibitors. PD-L1 expression in tumour cells or TILs predicts longer disease free survival and demonstrates temperospatial heterogeneity. Disciplines Medicine and Health Sciences Publication DetailsRoper, E., Lum, T., Palme, C. E., Ashford, B., Ch'ng, S.

show abstract

Section: Discussionmentioning

confidence: 99%

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A recent analysis has shown a spatial discordance of tumor cell PD-L1 expression in 14% between lung cancers and brain metastasis, and a nonstatistical significant temporal discordance of 11% in samples tested for expression between 6 months apart. 19 Utilizing a categorical cut-off has proven difficult and there is currently no consensus for this. However, the current rationale for choosing cut-off for determining on treatment options remains unclear and may vary depending on type of tumor tissue that is being assessed.…”

Section: F I G U R E 2 Examples Of Pd-l1 Staining In Tumor Tissuesmentioning

confidence: 99%

PD‐L1 expression associated with worse survival outcome in malignant pleural mesothelioma

Nguyen

Montgomery

Fadia

et al. 2017

Asia-Pac J Clncl Oncology

View full text Add to dashboard Cite

Aim: There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome.Methods: Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity.Results: Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484).Conclusions: Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time.

show abstract

“…26 Advances in genetics have helped reveal the genetic complexity of melanoma and intratumoral heterogeneity. 27,28 In addition, TCR sequencing has shown that differences in T cell receptor residents within these lesions are greater than the genetic differences between individual metastases.…”

mentioning

confidence: 99%

Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

et al. 2017

View full text Add to dashboard Cite

Programmed death ligand 1 (PD-L1) expression represents a mechanism of immune escape by inhibiting T cell immunity. This study systematically evaluated the expression of PD-L1, spatial distribution of CD3 Moreover, type classification based on intratumoral CD3 infiltration and tumor cell PD-L1 expression was an independent prognostic factor for NPC patients. PD-L1 expression on tumor cells is a favorable prognosis factor in NPC patients with pre-existing intratumor-infiltrating lymphocytes.

show abstract

Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer

Cited by 291 publications

References 30 publications

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

PD‐L1 expression associated with worse survival outcome in malignant pleural mesothelioma

Tumor cells PD-L1 expression as a favorable prognosis factor in nasopharyngeal carcinoma patients with pre-existing intratumor-infiltrating lymphocytes

Contact Info

Product

Resources

About