Quantifying Tertiary Lymphoid Structure-Associated Genes in Formalin-Fixed Paraffin-Embedded Breast Cancer Tissues

Gu-Trantien, Chunyan; Garaud, Soizic; Migliori, Edoardo; Solinas, Cinzia; Lodewyckx, Jean Nicolas; Willard-Gallo, Karen

doi:10.1007/978-1-4939-8709-2_9

Cited by 6 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD20-CD3 IHC images were scanned and analyzed using HALO. Lymphoid niches were manually identified based on the presence of B cell (CD20 þ ) clusters and T cell (CD3 þ ) zones as described (22,23). Next, areas were measured in HALO and assigned as TLS (>60,000 mm 2 ) or lymphoid aggregate (LA; 10,000-60,000 mm 2 ; ref.…”

Section: Scoring Of Tlsmentioning

confidence: 99%

PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC

Hummelink

Noort

Muller

et al. 2022

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Durable clinical benefit to PD-1 blockade in NSCLC is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1T TILs, with predictive potential in NSCLC. Here, we examined PD-1T TILs as biomarker in NSCLC. Experimental Design: PD-1T TILs were digitally quantified in120 baseline samples from advanced NSCLC patients treated with PD-1 blockade. Primary outcome was Disease Control (DC) at 6 months. Secondary outcomes were DC at 12 months and survival. Exploratory analyses addressed the impact of lesion-specific responses, tissue sample properties and combination with other biomarkers on the predictive value of PD-1T TILs. Results: PD-1T TILs as a biomarker reached 77% sensitivity and 67% specificity at 6 months, and 93% and 65% at 12 months, respectively. Particularly, a patient group without clinical benefit was reliably identified, indicated by a high negative predictive value (NPV) (88% at 6 months, 98% at 12 months). High PD-1T TILs related to significantly longer progression-free (HR 0.39, 95% CI: 0.24-0.63, p<0.0001) and overall survival (HR 0.46, 95% CI: 0.28-0.76, p<0.01). Predictive performance was increased when lesion-specific responses and samples obtained immediately before treatment were assessed. Notably, the predictive performance of PD-1TTILs was superior to PD-L1 and TLS in the same cohort. Conclusions: This study established PD-1T TILs as predictive biomarker for clinical benefit to PD-1 blockade in advanced NSCLC patients. Most importantly, the high NPV demonstrates an accurate identification of a patient group without benefit.

show abstract

Section: Scoring Of Tlsmentioning

confidence: 99%

PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC

Hummelink

Noort

Muller

et al. 2022

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…New technologies are becoming available to separately analyze different cell types in cancer tissue, including immune cell subsets in the TIL (e.g., multiplex IHC, laser microdissection of selected regions for STP analysis). This may facilitate STP activity profiling in specific immune cell types in the TIL to investigate the relation with immunotherapy response (Gu-Trantien et al, 2018;Garaud et al, 2019;Solinas et al, 2019).…”

Section: Characterization Of the Immune Microenvironment And Blood Samplesmentioning

confidence: 99%

RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies

et al. 2021

Self Cite

View full text Add to dashboard Cite

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples. In contrast, the transcriptome contains information on signaling pathway activity and can complement genomic analyses. Here we present the validation and clinical application of a new knowledge-based mRNA-based diagnostic assay platform (OncoSignal) for measuring activity of relevant signaling pathways simultaneously and quantitatively with high resolution in tissue samples and circulating tumor cells, specifically with very small specimen quantities. The approach uses mRNA levels of a pathway’s direct target genes, selected based on literature for multiple proof points, and used as evidence that a pathway is functionally activated. Using these validated target genes, a Bayesian network model has been built and calibrated on mRNA measurements of samples with known pathway status, which is used next to calculate a pathway activity score on individual test samples. Translation to RT-qPCR assays enables broad clinical diagnostic applications, including small analytes. A large number of cancer samples have been analyzed across a variety of cancer histologies and benchmarked across normal controls. Assays have been used to characterize cell types in the cancer cell microenvironment, including immune cells in which activated and immunotolerant states can be distinguished. Results support the expectation that the assays provide information on cancer driving signaling pathways which is difficult to derive from next generation DNA sequencing analysis. Current clinical oncology applications have been complementary to genomic mutation analysis to improve precision medicine: (1) prediction of response and resistance to various therapies, especially targeted therapy and immunotherapy; (2) assessment and monitoring of therapy efficacy; (3) prediction of invasive cancer cell behavior and prognosis; (4) measurement of circulating tumor cells. Preclinical oncology applications lie in a better understanding of cancer behavior across cancer types, and in development of a pathophysiology-based cancer classification for development of novel therapies and precision medicine.

show abstract

“…Also, higher levels of “lymphocytic lobulitis” around TNBC than in non-TNBC have been described [ 14 ]. A role of lobules in TIL-homing and maybe maturity is also suggested by the fact that in the current series there were almost no cases with TLS, contrary to what is seen in DCIS and invasive cancer, where a higher number of cases with TLS is found [ 15 ]. Cases with lobular involution rarely had lymphocytes, which may reflect less immunogenicity with increasing age.…”

Section: Discussionmentioning

confidence: 69%

Infiltrating immune cells in benign breast disease and risk of subsequent invasive breast cancer

et al. 2021

View full text Add to dashboard Cite

Background It is well established that tumors are antigenic and can induce an immune response by the host, entailing lymphocytic infiltration of the tumor and surrounding stroma. The extent and composition of the immune response to the tumor, assessed through evaluation of tumor-infiltrating lymphocyte counts, has been shown in many studies to have prognostic and predictive value for invasive breast cancer, but currently, there is little evidence regarding the association between infiltrating immune cell counts (IICCs) in women with benign breast disease (BBD) and risk of subsequent invasive breast cancer. Methods Using a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest, we conducted a nested case-control study in which cases were women who developed a subsequent invasive breast cancer during follow-up and controls were individually matched to cases on age at BBD diagnosis. We assessed IICCs in normal tissue and in the BBD lesions, and we used unconditional logistic regression to estimate the multivariable odds ratios (OR) and 95% confidence intervals (CI) for the associations between IICCs and breast cancer risk. Results There was no association between the IICC in normal tissue (multivariable OR per 5% increase in IICC = 1.05, 95% CI = 0.96–1.16) or in the BBD lesion (OR per 5% increase in IICC = 1.06, 95% CI = 0.96–1.18) and risk of subsequent invasive breast cancer. Also, there were no associations within subgroups defined by menopausal status, BBD histology, BMI, and history of smoking. Conclusion The results of this study suggest that IICCs in BBD tissue are not associated with altered risk of subsequent invasive breast cancer.

show abstract

Quantifying Tertiary Lymphoid Structure-Associated Genes in Formalin-Fixed Paraffin-Embedded Breast Cancer Tissues

Cited by 6 publications

References 19 publications

PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC

PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC

RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies

Infiltrating immune cells in benign breast disease and risk of subsequent invasive breast cancer

Contact Info

Product

Resources

About