Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1) and strong immune-cell infiltration by TCD3 cells and macrophages

Vieira, T.; Antoine, Martine; Hamard, Cécile; Fallet, Vincent; Duruisseaux, M.; Rabbe, Nathalie; Rodenas, Anita; Cadranel, Jacques; Wislez, Marie

doi:10.1016/j.lungcan.2016.05.013

Cited by 122 publications

(136 citation statements)

References 28 publications

(65 reference statements)

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“…Immunotherapy targeting immune-checkpoint such as PD1/PD-L1 inhibitors might be of interest in this rare NSCLC subtype. PD-L1 expression in our study is high: from 53 to 90.2% as described in other studies [3,6–10]. PD-L1 expression in SC was found higher than in NSCLC in the same center with the same antibody and cutoff [3].…”

Section: Discussionsupporting

confidence: 82%

“…PD-L1 expression in our study is high: from 53 to 90.2% as described in other studies [3,6–10]. PD-L1 expression in SC was found higher than in NSCLC in the same center with the same antibody and cutoff [3]. In NSCLC, PD-L1 immunohistochemistry has emerged as a biomarker predicting which patients are more likely to respond to PD/PD-L1 blockade.…”

Section: Discussionsupporting

confidence: 80%

“…PD-L1 tumor positivity was defined as ≥5% tumor cell membrane staining like in other studies on PSCGCC [3,6]. The staining of immune cells by PD-L1 was not considered as a positive staining but only served as an internal positive control.…”

Section: Methodsmentioning

confidence: 99%

“…In NSCLC, PD-L1 expression is found either higher in squamous cell carcinoma than in adenocarcinoma or higher in adenocarcinoma than in squamous cell carcinoma[10+ [ref D’inceco,]. A recent study has showed that PD-L1 expression is more frequent in SC than in NSCLC [3]. …”

Section: Introductionmentioning

confidence: 99%

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PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis

et al. 2017

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Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis. Thirty-six patients who underwent surgical resection of a PSGSCC were included. PD-L1 (E1L3N) expression on tumor cells and PD1 (NAT105) expression by tumor infiltrating lymphocytes (TILs) were performed by immunohistochemistry. Results were compared to immunohistochemistry tests of TTF1, Napsin A, p40 and to molecular study of EGFR, KRAS, BRAF and HER2. Seventy-five % of PSCGCC were considered as positive for PD-L1.PD-L1 expression in PSGSCC is associated with TTF-1 and/or Napsin A expression (47.2%, p = 0.039). Few p40 positive PSCGCC expressed PD-L1 (8.3%, p = 0.013). PD1 expression was not related to TTF-1 and/or Napsin A expression (p = 0.47), p40 expression (p = 0.68) or survival (p = 0.14). PD-L1 or PD1 expression were not related to the age, gender, pT, pN, stage, visceral pleura invasion, histopathological subtype, the presence of giant cell component, the predominance of sarcomatoid component, and the presence of EGFR or BRAF or HER2 or PIK3CA mutation (p>0.05). PD-L1 expression was correlated with a worse overall survival in PSCGCC (p = 0.045). PD-L1 expression is frequent in PSCGCC and might be associated with the expression of adenocarcinoma markers (TTF-1, Napsin A) or the lack of expression of squamous cell carcinoma marker (p40).

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis

et al. 2017

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“…And a final score of 0–2 was considered as negative expression (−, noted as 0); 3–4: weak positive expression (+, noted as 1); 6–8: moderate positive expression (++, noted as 2); and 9–12 was strong positive expression (+++, noted as 3) (10). For PD-L1, based on previous studies, the samples with stained tumor cells < 5% was defined as negative (−, scored as 0) (20, 21). For PD-L1 positive ≥5% samples, the expression level were further classified into weak positive (+, noted as 1), moderate positive (++, noted as 2), and strong positive expression (+++, noted as 3) according to staining intensity from light brown to brown and dark brown, correspondingly (22).…”

Section: Methodsmentioning

confidence: 99%

Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

Wang

Wei

et al. 2017

Front. Immunol.

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Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4) plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4) levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041), increased clinical TNM stage (P < 0.001), and presence of lymphatic invasion (P < 0.001). Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = −0.485, P = 0.003). TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001). Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.

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Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology‐based cross‐organ study

Morisue,

Kojima,

Suzuki

et al. 2023

Intl Journal of Cancer

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Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non‐SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death‐ligand 1 (PD‐L1) expression. A total of 101 patients with SC or non‐SC (31 lung, 19 esophagus, 22 pancreas, 15 liver, 4 bile duct, 6 kidney, 2 uterus and 2 ovary) were identified among 7197 patients who underwent surgery at our institute (1997‐2020). SC was significantly associated with worse survival (HR: 1.571; 95% CI: 1.084‐2.277; P = .017). The frequency of postoperative progression within 6 months was significantly higher for SC patients (54% vs 28%; P = .002). The immune profiling revealed the densities of CD8+ T cells (130 vs 72 cells/mm2; P = .004) and tumor‐associated macrophages (566 vs 413 cells/mm2; P < .0001) and the tumor PD‐L1 expression score (40% vs 5%; P < .0001) were significantly higher in SCs than in non‐SCs. Among 73 SC patients with postoperative progression, multivariate Cox regression analysis showed that immunotherapy tended to be associated with favorable survival (HR: 0.256; 95% CI: 0.062‐1.057; P = .060). Collectively, SCs shared clinicopathological and immunological features across organs. Our study can initiate to standardize the pathological definition of SC and provide a rationale for the investigation and development for this rare disease in a cross‐organ manner.

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Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1) and strong immune-cell infiltration by TCD3 cells and macrophages

Abstract: PD-L1 expression was higher in SC than in NSCLC as well as immune-cell infiltration by TCD3 cells and macrophages. This suggests that targeting the PD-1/PD-L1 pathway could represent a new potential therapy.

Cited by 122 publications

References 28 publications

PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis

PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis

Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology‐based cross‐organ study

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