Programmed Cell Death Ligand 1 Expression in Resected Lung Adenocarcinomas: Association with Immune Microenvironment

Huynh, Tiffany G.; Morales-Oyarvide, Vicente; Campo, Meghan; Gainor, Justin F.; Bozkurtlar, Emine; Uruga, Hironori; Zhao, Liang; Gomez‐Caraballo, María; Hata, Aaron N.; Mark, Eugene J.; Lanuti, Michael; Engelman, Jeffrey A.; Mino‐Kenudson, Mari

doi:10.1016/j.jtho.2016.08.134

Cited by 80 publications

(73 citation statements)

References 48 publications

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“…It is also noticeable that the extent of staining increases from those tumours that are lepidic‐predominant to those that are acinar/papillary‐predominant to those are solid/micropapillary‐predominant. This result is in agreement with other studies showing that solid components of ADCs have high PD‐L1 expression . Our data also correlate with several studies on the importance of a predominant pattern for prognostication in resected ADCs, and, should a grading system based on a predominant pattern and pleomorphic features be implemented, this might have predictive value in relation to the response to immunomodulatory therapy, in similar fashion to solid/micropapillary patterns having relevance in relation to the response to conventional chemotherapy in an adjuvant setting …”

Section: Discussionsupporting

confidence: 92%

Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas

et al. 2018

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There are significant differences in PD-L1 expression in relation to histological patterns, with particularly high levels in those with pleomorphic features and low/undetectable levels in invasive mucinous adenocarcinomas and the lepidic components of non-mucinous adenocarcinomas. Assessment of PD-L1 expression in a resected adenocarcinoma with a lepidic component may therefore not be reliable when immumodulatory therapy for recurrent disease is being considered, and either re-biopsy or limiting assessment to the invasive component may be more appropriate.

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Section: Discussionsupporting

confidence: 92%

Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas

et al. 2018

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“…A fixed-effect model was employed due to no evident heterogeneity ( I 2 = 7%, P = 0.38), and the outcome revealed a significant correlation between PD-L1 expression and KRAS status (RR = 1.26; 95% CI, 1.06–1.50, P = 0.010, Figure 8A). Furthermore, the result mentioned above was obtained in the studies using PD-L1 McAbs (RR = 1.32; 95% CI, 1.06–1.65, P = 0.01, Figure 8B) [12, 13, 15, 16, 18]. However, subgroup analyses on the studies using PD-L1 PoAbs [14, 17, 21, 22] and on Chinese cohort studies [17, 18, 21, 22] displayed that no significant correlation between PD-L1 expression and KRAS status, (RR = 1.13; 95% CI, 0.87–1.48; P = 0.36, Figure 8C), (RR = 1.04; 95% CI, 0.74–1.47; P = 0.83, Figure 8D), respectively.…”

Section: Resultsmentioning

confidence: 69%

The correlation between programmed death-ligand 1 expression and driver gene mutations in NSCLC

et al. 2017

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ObjectivesThis study aimed to evaluate the correlation between positive PD-L1 expression and driver gene mutations in NSCLC and to seek preliminary evidence in favor of the strategy of PD-L1 inhibitors plus targeted agents.ResultsThe overall analyses revealed that positive PD-L1 expression had a significant relationship with KRAS status (RR = 1.26; 95% CI, 1.06−1.50, P = 0.010), but no correlation with clinical characteristics (gender, smoking status, histological types), driver gene status (EGFR, ALK) and overall survival (OS): male versus female (RR = 1.16; 95% CI, 0.95−1.42; P = 0.15), never smoking versus former/current smoking (RR = 0.79; 95% CI, 0.56−1.11; P = 0.17), adenocarcinoma versus non-adenocarcinoma (RR = 0.94; 95% CI, 0.63−1.41; P = 0.77), EGFR mutation versus EGFR wild type (RR = 0.74; 95% CI, 0.52−1.06; P = 0.10), ALK positive versus ALK negative (RR = 1.02; 95% CI, 0.75−1.38; P = 0.91), OS of positive PD-L1 expression versus that of negative PD-L1 expression (HR = 1.31, 95% CI, 0.90−1.90; P = 0.15), respectively. Noteworthily, subgroup analyses exhibited that in Chinese cohort studies, positive PD-L1 expression was significantly correlated with OS (HR = 1.75, 95% CI, 1.36−2.24, P < 0.0001); and in the studies using PD-L1 monoclonal antibodies (McAbs), positive PD-L1 expression was significantly correlated with KRAS mutation (RR = 1.32, 95% CI, 1.06−1.65, P = 0.01) and EGFR mutation (RR = 0.51, 95% CI, 0.28−0.93, P = 0.03).Materials and MethodsAfter thoroughly searching PubMed, EMBASE and Cochrane Library databases, 11 relevant studies incorporating 3128 cases were identified. The pooled data were analyzed via Review manager 5.3 software.ConclusionsPD-L1 inhibitors probably was a potential promising option to manage advanced NSCLC harboring KRAS mutation.

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“…In lung adenocarcinoma, the presence of KRAS or the absence of targetable mutation are associated with PD-L1 expression, whereas EGFR or other common mutated adenocarcinoma rarely express PD-L1 [17]. A study in SC found that KRAS mutations are associated with PD-L1 expression, probably because these mutations are more likely to occur in smokers [3].…”

Section: Discussionmentioning

confidence: 99%

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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Programmed Cell Death Ligand 1 Expression in Resected Lung Adenocarcinomas: Association with Immune Microenvironment

Cited by 80 publications

References 48 publications

Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas

Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas

The correlation between programmed death-ligand 1 expression and driver gene mutations in NSCLC

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

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