Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

Saab, Samer S.; Zalzale, Hussein; Rahal, Zahraa; Khalifeh, Yara; Sinjab, Ansam; Kadara, Humam

doi:10.3389/fimmu.2020.00159

Cited by 82 publications

(71 citation statements)

References 274 publications

(387 reference statements)

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“…Previously, spatial molecular changes have been documented in the local niche of LUAD including loss-of-heterozygosity in 3p and 9p, point mutations and tumor suppressor methylation (26,27). Earlier work also underscored transcriptome profiles, somatic driver variants, as well as genome-wide allelic imbalance that are shared between lung cancer and adjacent normal-appearing airway cells but that are absent in distant normal cells, thereby pointing to putative drivers of lung oncogenesis (4,5). As such, the interrogation of spatial dynamics in LUADs has been a topic of interest, particularly owing to its utility as a surrogate for studying difficult-to-obtain longitudinal patient (including precursor) samples.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have identified molecular alterations in histologically normal-appearing epithelial fields that are close to solid tumors including those of the lung and that are less prevalent or absent in relatively more distant (from the tumor) regions -- suggesting geospatial heterogeneity in the uninvolved lung that is pertinent to development of a nearby tumor (4). While these studies have provided valuable insights into the spatial development of cancer from a particular niche in the lung, they have been mainly guided by bulk profiling approaches (4,5). It is now appreciated that editing of the immune microenvironment towards protumor phenotypes including escape of immune surveillance portends the underlying biology, development, and progression of LUAD (5).…”

Section: Introductionmentioning

confidence: 99%

“…While these studies have provided valuable insights into the spatial development of cancer from a particular niche in the lung, they have been mainly guided by bulk profiling approaches (4,5). It is now appreciated that editing of the immune microenvironment towards protumor phenotypes including escape of immune surveillance portends the underlying biology, development, and progression of LUAD (5). Yet, the interplay between individual immune cell populations (and other cell subsets) in spatial development of early-stage LUAD is not known.…”

Section: Introductionmentioning

confidence: 99%

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Resolving the spatial and cellular architecture of lung adenocarcinoma by multi-region single-cell sequencing

Sinjab

Han

Kobayashi

et al. 2020

Preprint

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Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and fourteen multi-region normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to the LUADs. LUADs exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs driven by KRAS mutations. T regulatory cell phenotypes are increased in normal tissues with closer proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages and inflammatory dendritic cells. Further, the LUAD ecosystem harbors gain of ligand-receptor based interactions involving increased expression of CD24 antigen on epithelial cells and SIGLEC10 on myeloid subsets. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Resolving the spatial and cellular architecture of lung adenocarcinoma by multi-region single-cell sequencing

Sinjab

Han

Kobayashi

et al. 2020

Preprint

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“…Some of the viruses that are being considered for this type of immunotherapy are from the herpes simplex family, such as fowlpox virus, Newcastle disease virus, reovirus and measles virus (MV), but some adenoviruses, picornaviruses (including coxsackie), reovirus, maraba, vaccinia virus, retroviruses and mumps are also considered [ 35 , 36 , 37 ]. In 2015, the FDA approved talimogene laherparepvec (T-VEC or Imlygic), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with Granulocyte Macrophage colony-stimulating factor (GM-CSF) [ 34 ], for the treatment of metastatic melanoma, which was the first approved oncolytic viral immunotherapy, although there are several clinical trials of oncolytic viruses that cover almost all solid tumors, including lung cancer.…”

Section: Immunotherapy For Lung Cancermentioning

confidence: 99%

Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy

Boyero

Sánchez-Gastaldo

Alonso

et al. 2020

Cancers

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After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field. The appearance of immunotherapy, especially immune checkpoint inhibitors, has improved both the overall survival and quality of life of patients, many of whom are diagnosed late when classical treatments are ineffective. Despite these unprecedented results, a high percentage of patients do not respond initially to treatment or relapse after a period of response. This is due to resistance mechanisms, which require understanding in order to prevent them and develop strategies to overcome them and increase the number of patients who can benefit from immunotherapy. This review highlights the current knowledge of the mechanisms and their involvement in resistance to immunotherapy in lung cancer, such as aberrations in tumor neoantigen burden, effector T-cell infiltration in the tumor microenvironment (TME), epigenetic modulation, the transcriptional signature, signaling pathways, T-cell exhaustion, and the microbiome. Further research dissecting intratumor and host heterogeneity is necessary to provide answers regarding the immunotherapy response and develop more effective treatments for lung cancer.

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“… 8 Evidence shows that the use of immunotherapy has led to unprecedented survival benefits especially compared to treatment with chemotherapy alone in selected patients. The breakthroughs in immunotherapy have greatly benefited a subset of lung cancer patients, not only the NSCLC, but also the extensive-stage SCLC, 9 and the most important is that they are bringing forth a paradigm shift in the drugs approved for cancer treatment 10 Antibody-drug conjugate therapy, another anti-PD-1/PD-L1 therapy, has been widely concerned. Antitumor activity of lung cancer has been accomplished by conjugating antibodies with different effector molecules that accomplish cell death after antibody binding and internalisation.…”

Section: Introductionmentioning

confidence: 99%

The Top 100 Most Frequently Cited Publications Concerning Anti-PD-1/PD-L1 Therapy for Lung Cancer: A Bibliometric Analysis

Li¹,

Lv²,

Liu³

et al. 2021

CMAR

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Background Globally lung cancer is one of the most common cancers, and is responsible for almost 20% of all cancer care costs. As a potential treatment for lung cancer, anti-PD-1/PD-L1 therapy has become a novel scientific hotspot in recent decades. The present study aims at exploring the status and trends of the top frequently cited publications about the anti-PD-1/PD-L1 therapy for lung cancer via bibliometric analysis. Methods The publications concerning anti-PD-1/PD-L1 therapy for lung cancer were searched on the core collection database of Web of Science, setting the time period for retrieval from 1950 to 2019. The top 100 most frequently cited publications were retrieved, and the bibliometric data were mainly accessed through an open online analysis platform and VOSviewer software. Results The cited frequencies about the top 100 cited publications ranged from 218 to 6248. These articles were published in 39 publications, which were mainly ranked in Q1. The top journal in terms of the number of the articles was the New England Journal of Medicine (16 articles). The most frequently nominated author was Brahmer, JR from Sidney Kimmel Comprehensive Cancer Center, while the most contributing institution was Memorial Sloan Kettering Cancer. The United States acted as the pioneer in this new field of research and led plentiful of national and international co-operations. Immunotherapy, nivolumab, cell lung-cancer, safety, and docetaxel appeared more frequently as keywords. Discussions To sum up, high quality journals, influential authors and institutions and research with high quality evidence were apt to attract more attention and possess more public credibility. Moreover, the bibliometric analysis is yielding up its advantage of identifying and analyzing the characteristics and changes in the intellectual structures of a special topic.

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Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

Cited by 82 publications

References 274 publications

Resolving the spatial and cellular architecture of lung adenocarcinoma by multi-region single-cell sequencing

Resolving the spatial and cellular architecture of lung adenocarcinoma by multi-region single-cell sequencing

Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy

The Top 100 Most Frequently Cited Publications Concerning Anti-PD-1/PD-L1 Therapy for Lung Cancer: A Bibliometric Analysis

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