Composition of the immune microenvironment differs between carcinomas metastatic to the lungs and primary lung carcinomas

Senarathne, Wijendra; Vranić, Semir; Xiu, Joanne; Rose, Inga; Gates, Peggy; Gatalica, Zoran

doi:10.1016/j.anndiagpath.2017.12.004

Cited by 4 publications

(8 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Resultsmentioning

confidence: 99%

“…A total of 14 publications reporting the association of TMB with biomarkers were identified (Table 3) [10, 27, 36, 45–55]. Nine publications reported data on PD-L1 and TMB [10, 27, 36, 45, 48–50, 53, 55]. Four reported significant associations of PD-L1 and TMB [45, 48, 53, 55], with two reporting weak Spearman’s correlations of 0.12 and 0.085 [45, 48].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Tumor mutational burden in lung cancer: a systematic literature review

et al. 2019

View full text Add to dashboard Cite

Purpose: To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. Results: In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with TP53 alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. Methods: A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE®, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. Conclusion: This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Tumor mutational burden in lung cancer: a systematic literature review

et al. 2019

View full text Add to dashboard Cite

show abstract

“…46 altered loci, as previously reported. [17][18][19] Gene copy number variations were identified by comparing the depth of NGS sequence reads to reads from a diploid control. Genes with !…”

Section: Next-generation Sequencing (Ngs)mentioning

confidence: 99%

“…6 copies were considered amplified. 17,18 ArcherDx FusionPlex Assay (ArcherDX, Boulder, CO) was used to explore gene fusions. Fifty-three gene targets were analyzed in 12 NECs.…”

Section: Next-generation Sequencing (Ngs)mentioning

confidence: 99%

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Vranić

Palazzo

Sanati

et al. 2019

Clinical Breast Cancer

Self Cite

View full text Add to dashboard Cite

Neuroendocrine breast cancer lacks specific therapy, but similar common neuroendocrine carcinomas may offer guidance for therapy development. This study, for the first time, identified several biomarkers for targeted therapy approaches in patients with breast neuroendocrine carcinoma. Introduction: Neuroendocrine carcinoma (NEC) of the breast is a rare, special type of breast cancer, reportedly constituting 2% to 5% of all breast cancers. Although breast NEC does not have a specific targeted therapy, several new targeted therapies based on specific biomarkers were recently investigated in the NEC of lung and in other types of breast carcinoma, which may provide guidance to their feasibility in breast NEC. Materials and Methods: Twenty breast NECs were profiled for biomarkers of therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Results: Predictive expression of TROP-2, FOLR1, and H3K36Me3 were detected in different subsets of tumors and may pave the way for development of novel targeted therapies in some patients with breast NECs. There was no evidence of DLL3 expression, NTRK gene fusions, or MGMT hypermethylation. No biomarkers predictive of immune checkpoint inhibitor efficacy (programmed death-ligand 1 expression, tumor mutational burden, microsatellite instability) were identified. FGFR and CCND1 gene amplifications were detected in isolated cases. Conclusions: This study identified several potential targets for novel therapies in breast NEC, including farletuzumab and mirvetuximab soravtansine (FOLR1), sacituzumab govitecan (TROP-2), and HDAC inhibitors (H3K36Me3). In some cases, CCND1 gene amplification may indicate the usefulness of investigational therapies. The reported results should serve as an early indication of potential clinical relevance in selected patients with breast NEC.

show abstract

“…Such tumor microenvironment facilitates the proliferation of tumor cells. Many studies have shown successful outcomes of PD-1 and PD-L1 targeting immunotherapies in non-small cell lung carcinomas (NSCLC) [1][2][3][4][5][6][7]. Moreover, Liu et al reported an increased survival rate in glioblastoma multiforme patients with upregulated PD-L1 expression in neurons adjacent to tumors [8].…”

Section: Concordance Of Pd-l1 Expression and Cd8 + Til Intensitymentioning

confidence: 99%

Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases

Batur

Dülger

DURAK

et al. 2019

Bosn J of Basic Med Sci

View full text Add to dashboard Cite

Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1–49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1–49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.

show abstract

Composition of the immune microenvironment differs between carcinomas metastatic to the lungs and primary lung carcinomas

Cited by 4 publications

References 39 publications

Tumor mutational burden in lung cancer: a systematic literature review

Tumor mutational burden in lung cancer: a systematic literature review

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases

Contact Info

Product

Resources

About