Tumor-Associated Tertiary Lymphoid Structures: Gene-Expression Profiling and Their Bioengineering

Zhu, Genyuan; Falahat, Rana; Wang, Kui; Mailloux, Adam W.; Artzi, Natalie; Mulé, James J.

doi:10.3389/fimmu.2017.00767

Cited by 41 publications

(32 citation statements)

References 47 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we explored whether the results would differ in groups of patients with unique features. Finally, we found that LRH is associated with better PFS in patients with a BMI greater than 24 kg/m 2 , which was in agreement with previous research ( 34 ). The reason for this can be explained in that overweight is associated with more postoperative complications by ARH, such as poor healing of the incision and a high rate of postoperative ileus.…”

Section: Discussionsupporting

confidence: 93%

A Comparison of Laparoscopies and Laparotomies for Radical Hysterectomy in Stage IA1-IB1 Cervical Cancer Patients: A Single Team With 18 Years of Experience

Qin

Huang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Objective To investigate the safety and efficacy of abdominal radical hysterectomy (ARH) and laparoscopic radical hysterectomy (LRH) in managing early-stage cervical cancer. Methods This retrospective study comprised patients with FIGO stage IA1 with lymphovascular space invasion (LVSI), IA2, and IB1 cervical cancer who underwent radical hysterectomy performed by a single gynecologic oncology team at Peking Union Medical College Hospital from 2000–2018. The clinicopathological characteristics, surgical outcomes, and survival outcomes were compared between the two groups. Results The ARH and LRH groups consisted of 84 and 172 patients, respectively. The 5-year progression-free survival (PFS) rates were 89.3 and 95.9% in the ARH and LRH groups ( P = 0.122, adjusted HR = 0.449, 95% CI: 0.162–1.239), respectively, while the 5-year overall survival (OS) rates were 95.2 and 98.8%, respectively ( P = 0.578, adjusted HR = 0.650, 95% CI: 0.143–2.961). The presence of more than two comorbidities led to poor OS ( P = 0.011). For patients with a BMI greater than 24 kg/m 2 , LRH was associated with better PFS ( P = 0.039). Compared with ARH, LRH was associated with a shorter operation time (248.8 vs. 176.9 min, P < 0.001), less blood loss (670.2 vs. 200.9 ml, P < 0.001), and lower postoperative ileus rates (2.4% vs. 0%, P = 0.042). No significant differences were observed in PFS and OS between 2006–2012, 2013–2015, and 2016–2018 in the LRH group ( P = 0.126 and P = 0.583). Conclusion Compared with ARH, LRH yields similar survival and improved surgical outcomes in patients with early-stage cervical cancer. LRH is not inferior to ARH for select cervical cancer patients treated by a single team with adequate laparoscopy experience.

show abstract

Section: Discussionsupporting

confidence: 93%

A Comparison of Laparoscopies and Laparotomies for Radical Hysterectomy in Stage IA1-IB1 Cervical Cancer Patients: A Single Team With 18 Years of Experience

Qin

Huang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Immune cell heterogeneity within tumors may contribute to decreased associations between gene expression analysis and IHC quantification 40 . In particular, collections of immune cells present not within the tumor itself but within tertiary lymphoid structures (TLS) on the peripheral margins of tumor 42 , 43 may have been represented by the gene expression analyses, but not by IHC of tumor cores taken from the center of tumor nodules. Other possible factors that could impact association between gene expression and IHC analysis are differences in time course for preservation of each tumor specimen and the length of time each specimen was stored, especially if protein is more stable than mRNA.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis in formalin fixed paraffin embedded melanomas is associated with density of corresponding immune cells in those tissues

Kwak

Erdag

Slingluff

2020

Sci Rep

View full text Add to dashboard Cite

Immune cell infiltrates in melanoma have important prognostic value. Gene expression analysis may simultaneously quantify numbers and function of multiple immune cell subtypes in formalin-fixed paraffin-embedded (FFPE) tissues. Prior studies report single gene expression can represent individual immune cell subtypes, but this has not been shown in FFPE melanomas. We hypothesized that gene expression profiling of human melanomas using a new RNA expression technology in FFPE tissue would correlate with the same immune cells identified by immunohistochemistry (IHC). This retrospective study included melanoma specimens analyzed by IHC on tumor tissue microarray (TMA) cores and by gene expression profiling with EdgeSeq Immuno-Oncology Assay using qNPA technology on the corresponding tumors. Standardized gene expression levels were analyzed relative to enumerated cells by IHC using Spearman rank test to calculate r-values. Multivariate analysis was performed by Kruskal–Wallis test. 119 melanoma specimens had both IHC and gene expression information available. There were significant associations between the level of gene expression and its quantified IHC cell marker for CD45+, CD3+, CD8+, CD4+, and CD20+ cells (all p < 0.001). There were also significant associations with exhaustion markers FoxP3+, PD-1+, and PD-L1+ (all p ≤ 0.0001). This new qNPA technology is useful to quantify intratumoral immune cells on FFPE specimens through RNA gene expression in metastatic melanoma. As previous studies have shown on other solid human tumors, we also confirm that the expression level of a single gene may be used to represent a single IHC immune cell marker in melanoma.

show abstract

“…In addition, we describe the ability of a TLR9 agonist to induce neogenesis of TLSs, composed of highly compacted B cells, DCs, and T cells in close contact, adjacent to lung tumors. TLSs are correlated with long-term survival in multiple human cancers, including NSCLC, and likely function as the site of initiation and maintenance of humoral and T-cell response against tumor antigens (30,40). Similarly, de novo TLSs have been demonstrated to function as priming sites of T cells in the lung after mucosal immunization (41).…”

Section: Discussionmentioning

confidence: 99%

Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade by Promoting Optimal CD4+ and CD8+ T-cell Interplay

et al. 2018

View full text Add to dashboard Cite

Currently approved inhibitors of the PD-1/PD-L1 pathway represent a major advance for the treatment of lung cancers, yet they are ineffective in a majority of patients due to lack of preexisting T-cell reactivity. Here, we show that a TLR9 agonist delivered by inhalation is able to prime T-cell responses against poorly immunogenic lung tumors and to complement the effects of PD-1 blockade. Inhaled TLR9 agonist causes profound remodeling in tumor-bearing lungs, leading to the formation of tertiary lymphoid structures adjacent to the tumors, CD8 T-cell infiltration into the tumors, dendritic cell expansion, and antibody production. Inhalation of TLR9 agonist also increased the pool of functional PD-1T-bet effector CD8 T cells in tumor-bearing lungs. Effector CD8 T cells generated by inhaled TLR9 agonist treatment were licensed by PD-1 blockade to become highly functional CTLs, leading to a durable rejection of both lung tumors and tumor lesions outside the lungs. CD4 T cells activated in response to inhaled TLR9 play a critical role in this process by controlling the proliferation, preventing exhaustion, and guiding the differentiation of optimally functional CTLs. This study characterizes a strategy to apply localized TLR9 stimulation to a tumor type not accessible for direct injection, a strategy that may expand the therapeutic potential of PD-1 blockade in non-small cell lung cancer. These findings demonstrate that local delivery of a toll-like receptor 9 agonist can change the immune content of an entire organ and enhance the efficacy of immune checkpoint inhibition. http://cancerres.aacrjournals.org/content/canres/78/17/4943/F1.large.jpg .

show abstract

Tumor-Associated Tertiary Lymphoid Structures: Gene-Expression Profiling and Their Bioengineering

Cited by 41 publications

References 47 publications

A Comparison of Laparoscopies and Laparotomies for Radical Hysterectomy in Stage IA1-IB1 Cervical Cancer Patients: A Single Team With 18 Years of Experience

A Comparison of Laparoscopies and Laparotomies for Radical Hysterectomy in Stage IA1-IB1 Cervical Cancer Patients: A Single Team With 18 Years of Experience

Gene expression analysis in formalin fixed paraffin embedded melanomas is associated with density of corresponding immune cells in those tissues

Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade by Promoting Optimal CD4+ and CD8+ T-cell Interplay

Contact Info

Product

Resources

About