Genomic Landscape and Immune Microenvironment Features of Preinvasive and Early Invasive Lung Adenocarcinoma

Chao, Zhang; Zhang, Jianjun; Xu, Fang; Wang, Yin Guang; Xie, Zhi; Su, Jian; Dong, Song; Nie, Qiang; Shao, Yang; Zhou, Qing; Yang, Jin; Yang, Xue; Zhang, Xu-Chao; Li, Zhi; Wu, Yi‐Long; Zhong, Wen Zhao

doi:10.1016/j.jtho.2019.07.031

Cited by 129 publications

(130 citation statements)

References 42 publications

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“…However, Castagnola et al also demonstrated that aneuploidy, global genomic derangement (measured as the total number of Copy Number Alterations, CNAs), and specific focal CNAs are present early in the evolution of oral cancer and are more frequent at later stages [73]. These results are in accordance with Zhang et al, who showed that, before the acquisition of invasion, immunoediting and intratumor genomic heterogeneity are early events that may happen [77]. Interestingly, Gu et al showed that, in the tumor-free tongue of patients with SCCOT, the cytolytic activity has clinical relevance rather than the levels of immune infiltration or degree of cytolytic activity within the tumor [78].…”

Section: Mutational Load and Immunology: Should These Factors Be Analsupporting

confidence: 56%

“…However, the vast increase in knowledge resulting from cancer research in recent decades made it possible to identify with greater accuracy the varying degrees of disparate genetic, molecular, transcriptomic, and immunologic profiles that characterize preneoplastic lesions. Some therapeutic strategies for the molecular cancer prevention are the use of natural or synthetic compounds that stop the prime drivers, key imbalances, or the context in which these drivers act and in which the derangements occur, prior to invasion across the basement membrane [11,77,106,107]. Among therapies targeting head and neck cancer, immunotherapy has gained attention in recent years, not only for treatments of advanced diseases but also as molecular prevention therapy [11,77,106,107].…”

Section: Resultsmentioning

confidence: 99%

“…Some therapeutic strategies for the molecular cancer prevention are the use of natural or synthetic compounds that stop the prime drivers, key imbalances, or the context in which these drivers act and in which the derangements occur, prior to invasion across the basement membrane [ 11 , 77 , 106 , 107 ]. Among therapies targeting head and neck cancer, immunotherapy has gained attention in recent years, not only for treatments of advanced diseases but also as molecular prevention therapy [ 11 , 77 , 106 , 107 ]. However, except for the HPV vaccination for oro-pharyngeal cancers, despite their conceptual promise, the efficacy of immunoprevention of oral cancer is not currently demonstrated.…”

Section: Resultsmentioning

confidence: 99%

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Leukoplakia and Immunology: New Chemoprevention Landscapes?

Grigolato

Bizzoca

Calabrese

et al. 2020

IJMS

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Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.

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Section: Mutational Load and Immunology: Should These Factors Be Analsupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Leukoplakia and Immunology: New Chemoprevention Landscapes?

Grigolato

Bizzoca

Calabrese

et al. 2020

IJMS

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“…Our results follow these findings suggesting that the localization of CD8 positive cells is more frequently found in the epithelium +/− the submucosa; whereas CD8 positive cells are only located in the submucosa when no medical history of squamous cell carcinoma was found. For atypical adenomatous hyperplasia, which is the pre-invasive counterpart of bronchial dysplasia for lung adenocarcinoma, it has recently been shown that tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Escape Is an Early Event in Pre-Invasive Lesions of Lung Squamous Cell Carcinoma

et al. 2020

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Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma.

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“…15,16 With the maturity of high-throughput technology and the development of many algorithms aimed at studying tumor immunity (single sample Gene Set Enrichment Analysis [ssGSEA], quanTIseq, CIBERSORT, etc), [17][18][19] it is possible to describe the landscape of tumor immune microenvironment (TME) through transcriptome sequencing. 20,21 However, no studies have systematically delineated the TME in BCa. We constructed an immune signature of 13-mRNA based on the least absolute shrinkage and selection operator (LASSO) algorithm and then, the TME landscape of BCa was depicted according to two currently popular algorithms and quantitatively estimated the main immune cells, thus finding a significant correlation between immune signature score (ISS) and immune escape phenotype.…”

Section: Introductionmentioning

confidence: 99%