Immunogenomic profiling of lung adenocarcinoma reveals poorly differentiated tumors are associated with an immunogenic tumor microenvironment

Akhave, Neal S.; Zhang, Jiexin; Bayley, Erin M.; Frank, Meredith; Chiou, Shin-Heng; Behrens, Carmen; Chen, Runzhe; Hu, Xin; Parra, Edwin R.; Lee, Won‐Chul; Swisher, Stephen G.; Solis, Luisa M.; Weissferdt, Annikka; Moran, César A.; Kalhor, Neda; Zhang, Jianhua; Scheet, Paul; Vaporciyan, Ara A.; Sepesi, Boris; Gibbons, Don L.; Heymach, John V.; Lee, John; Wistuba, Ignacio I.; Futreal, P. Andrew; Zhang, Jianjun; Fujimoto, Junya; Reuben, Alexandre

doi:10.1016/j.lungcan.2022.08.007

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…The cervical cancer tissue microarray sample immunohistochemistry analysis performed by Saglam et al showed that PD-L1 expression was higher in poorly differentiated tumors than in moderately differentiated tumors [ 27 ]. The expression of PD-L1 was usually higher in poorly differentiated tumors; this finding has been reported for several other cancers, such as non-small cell lung carcinoma [ 28 , 29 ], thyroid cancer [ 30 ] and gallbladder cancer [ 31 ]. In our study, the degree of tumor differentiation was a negative independent predictor for PD-L1 status in the binary multivariate logistic regression analysis.…”

Section: Discussionsupporting

confidence: 64%

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Pang

Song

et al. 2023

Diagnostics

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Background: Immunotherapy targeting PD-1/PD-L1 has been proven to be effective for cervical cancer treatment. To explore non-invasive examinations for assessing the PD-L1 status in cervical cancer, we performed a retrospective study to investigate the predictive value of 18F-FDG PET/CT. Methods: The correlations between PD-L1 expression, clinicopathological characteristics and 18F-FDG PET/CT metabolic parameters were evaluated in 74 cervical cancer patients. The clinicopathological characteristics included age, histologic type, tumor differentiation, FIGO stage and tumor size. The metabolic parameters included maximum standard uptake (SUVmax), mean standard uptake (SUVmean), total lesion glycolysis (TLG) and tumor metabolic volume (MTV). Results: In univariate analysis, SUVmax, SUVmean, TLG, tumor size and tumor differentiation were obviously associated with PD-L1 status. SUVmax (rs = 0.42) and SUVmean (rs = 0.40) were moderately positively correlated with the combined positive score (CPS) for PD-L1 in Spearman correlation analysis. The results of multivariable analysis showed that the higher SUVmax (odds ratio = 2.849) and the lower degree of differentiation (Odds Ratio = 0.168), the greater probability of being PD-L1 positive. The ROC curve analysis demonstrated that when the cut-off values of SUVmax, SUVmean and TLG were 10.45, 6.75 and 143.4, respectively, the highest accuracy for predicting PD-L1 expression was 77.0%, 71.6% and 62.2%, respectively. The comprehensive predictive ability of PD-L1 expression, assessed by combining SUVmax with tumor differentiation, showed that the PD-L1-negative rate was 100% in the low probability group, whereas the PD-L1-positive rate was 84.6% in the high probability group. In addition, we also found that the H-score of HIF-1α was moderately positively correlated with PD-L1 CPS (rs = 0.51). Conclusions: The SUVmax and differentiation of the primary lesion were the optimum predictors for PD-L1 expression in cervical cancer. There was a great potential for 18F-FDG PET/CT in predicting PD-L1 status and selecting cervical cancer candidates for PD1/PD-L1 immune checkpoint therapy.

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Section: Discussionsupporting

confidence: 64%

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Pang

Song

et al. 2023

Diagnostics

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“…Specifically, we showed that PD‐L1 expression is observed in a non‐negligible (23.5%) subset of G2 tumours and is correlated with poor prognosis. Although this subset may correspond to both aggressive and immunogenic subset among G2 tumours, 27 it remains uncertain whether these tumours derive similar benefits from adjuvant immunotherapy as PD‐L1‐positive G3 tumours. In future trials, subgroup analyses would provide more granular indications on adjuvant immunotherapy based on tumour histologic grade and PD‐L1 status.…”

Section: Discussionmentioning

confidence: 99%

PD‐L1 expression in resected lung adenocarcinoma: prevalence and prognostic significance in relation to the IASLC grading system

Hwang,

Hong,

Kim

et al. 2024

Histopathology

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AimsProgrammed death‐ligand 1 (PD‐L1) expression is a predictive biomarker for adjuvant immunotherapy and has been linked to poor differentiation in lung adenocarcinoma. However, its prevalence and prognostic role in the context of the novel histologic grade has not been evaluated.MethodsWe analysed a cohort of 1233 patients with resected lung adenocarcinoma where PD‐L1 immunohistochemistry (22C3 assay) was reflexively tested. Tumour PD‐L1 expression was correlated with the new standardized International Association for the Study of Lung Cancer (IASLC) histologic grading system (G1, G2, and G3). Clinicopathologic features including patient outcome were analysed.ResultsPD‐L1 was positive (≥1%) in 7.0%, 23.5%, and 63.0% of G1, G2, and G3 tumours, respectively. PD‐L1 positivity was significantly associated with male sex, smoking, and less sublobar resection among patients with G2 tumours, but this association was less pronounced in those with G3 tumours. PD‐L1 was an independent risk factor for recurrence (adjusted hazard ratio [HR] = 3.25, 95% confidence intervals [CI] = 1.93–5.48, P < 0.001) and death (adjusted HR = 2.69, 95% CI = 1.13–6.40, P = 0.026) in the G2 group, but not in the G3 group (adjusted HR for recurrence = 0.94, 95% CI = 0.64–1.40, P = 0.778).ConclusionPD‐L1 expression differs substantially across IASLC grades and identifies aggressive tumours within the G2 subgroup. This knowledge may be used for both prognostication and designing future studies on adjuvant immunotherapy.

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“…acinar. 39 Another report states that among the five major subtypes, the acinar subtype has the highest number of CD4+ T cells. 14…”

Section: Discussionmentioning

confidence: 99%

Differential Gene Expression of Tumors Undergoing Lepidic-Acinar Transition in Lung Adenocarcinoma

Okoshi,

Fujita,

Lami

et al. 2024

Preprint

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Lung adenocarcinoma is the most frequent subtype of thoracic malignancy, which is itself the largest contributor to cancer mortality. The lepidic subtype is a non-invasive tumor morphology, whereas the acinar subtype represents one of the invasive morphologies. This study investigates the transition from a non-invasive to an invasive subtype in the context of lung adenocarcinoma.Patients with pathologically confirmed mixed subtype tumors consented to analysis of RNA-seq data extracted from each subtype area separately.The study included 17 patients with tumors found to exhibit a lepidic-acinar transition. 87 genes were found to be differentially expressed between the lepidic and acinar subtypes, with 44 genes significantly upregulated in lepidic samples, and 43 genes significantly upregulated in acinar samples. Gene ontology analysis showed that many of the genes upregulated in the acinar subtype were related to immune response. Immune deconvolution analysis showed that there was a significantly higher proportion of M1 macrophages and total B cells in acinar areas. Immunohistochemistry showed that B cells were mainly localized to tertiary lymphoid structures in the tumor area.This is the first study to investigate the molecular features of mixed subtype lepidic-acinar transitional tumors. Immunological dynamics are presumed to be involved in this transition from lepidic to acinar subtype. Further research should be conducted to elucidate the progression of disease from non-invasive to invasive morphologies.

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Immunogenomic profiling of lung adenocarcinoma reveals poorly differentiated tumors are associated with an immunogenic tumor microenvironment

Cited by 10 publications

References 51 publications

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

Retrospective Analysis of the Predictive Value of 18F-FDG PET/CT Metabolic Parameters for PD-L1 Expression in Cervical Cancer

PD‐L1 expression in resected lung adenocarcinoma: prevalence and prognostic significance in relation to the IASLC grading system

Differential Gene Expression of Tumors Undergoing Lepidic-Acinar Transition in Lung Adenocarcinoma

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