A strong expertise in tertiary lymphoid structure (TLS) detection & evaluation by digital pathology

Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression

Nature Cancer, 2021

Mature TLS predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression

Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort

Nature Medicine, 2022

Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort

Upregulation of Indoleamine 2,3-Dioxygenase 1 in Tumor Cells and Tertiary Lymphoid Structures is a Hallmark of Inflamed Non-Small Cell Lung Cancer

Clinical Cancer Research, 2023

Upregulation of IDO1 in tumor cells and Tertiary Lymphoid Structures is a hallmark of inflamed Non–Small Cell Lung Cancer

TLS scoring to progress precision cancer immunotherapy

tissue processing-digital pathology-histopathology CRO services

Processing of tumor specimens

  • Eligible samples: formalin-fixed paraffin-embedded (FFPE) tumor tissues specimens
  • Source: provided by sponsor or acquired by our team
  • In-house capacities: fixation, paraffin embedding, slicing & slide preparation, H&E coloration & annotation by trained pathologists
automated staining ventana CRO services histopathology

Multiplexed TLS imaging

  • In-house validated panels (IHF & IHC-based) to evaluate TLS presence & maturity
  • Automated staining with Ventana Discovery XTTM systems
  • Large-capacity multispectral imaging with PhenoImagerTM systems
digital pathology image analysis immuno-oncology CRO services

Expert pathologists for TLS scoring

  • Expert pathologists to determine TLS presence & maturity status using serial IHF/IHC & HES images
  • Extensive experience in TLS scoring with > 10,000 cases already evaluated across different tumor types
  • Delivery of a TLS report per case (request sample report)

In Nature Cancer: correlating TLS presence with cancer immunotherapy efficacy & clinical outcome

Assessment of the presence of TLS and their maturation stage in tumors

Illustration of a mature TLS detected in a primary pancreatic adenocarcinoma.

mature TLS scoring by digital imaging IHC IF

Illustration of an immature TLS detected in a primary lung adenocarcinoma.

immature TLS detectionby digital-pathology IHC / IF CRO service

This panel shows representative examples of immature and mature TLS observed in tumor samples. The pictures from the left to right column correspond to 1) Hematoxylin Eosin Saffron (HES) staining, 2) Double immunohistochemistry staining of CD3/CD20 (CD3 in brown, CD20 in purple), 3) Multiplex immunofluorescence assay of CD4 (blue), CD8 (yellow), CD20 (orange), CD21 (green) and CD23 (pink). The scale bars on the HES images indicate 50µm and 100µm for the upper and lower panels, respectively. Black cropped arrows highlight the tumor cells in the samples.

Mature TLSs are predictive of outcome in patients with cancer treated with immune checkpoint inhibitors

Mature TLS as a predictive biomarker of cancer immunotherapy

The presence and maturity of TLSs were assessed in TLS-positive tumors using a multiplex immunofluorescence assay combining CD4, CD8, CD20, CD21 and CD23 markers. The results are representative of 540 tumors analyzed. Left: Response rate, as defined per RECIST 1.1 criteria, according to TLS status: absence (no TLSs; n = 223 patients), iTLSs (n = 21 patients) or mTLSs (n = 84 patients). OR, objective response; PD, progressive disease; SD, stable disease. Statistical significance was determined by chi-squared test. Middle and right: Kaplan–Meier curves of progression-free survival and overall survival in the discovery cohort of 328 patients with cancer who were treated with anti-PD-1 or anti-PD-L1 antagonists according to mTLS status (red curve: mTLS-enriched tumors; blue curve: mTLS-negative tumors). Numbers below each x-axis indicate the number of patients at risk and those in parentheses are the number of events. Statistical significance was determined by log-rank test).

Your contacts

explicyte team 2024

Talk to our team !

Paul Marteau, PharmD (preclinical study director), Imane Nafia, PhD (CSO), Loïc Cerf, MSc (COO), Alban Bessede, PhD (founder, CEO), Jean-Philippe Guégan, PhD (translational study director)

Tell us about your project !

    Select department:

    TLS Detection & Scoring for Cancer Immunotherapy

    In the past few years, conjointly with teams from Institut Bergonié (Pr Antoine ITALIANO, Dr Lucile VANHERSECKE), Explicyte Immuno-Oncology released papers in Nature Cancer, Laboratory Investigation, and Nature Medicine, highlighting the importance of TLS analysis in the context of cancer immunotherapies. We thus developed a multiplexed panel to detect TLS presence and maturity status to ultimately select patients who might benefit the most from cancer immunotherapies. Based on in-house capacities in digital pathology (from sample preparation to automated acquisition and scoring), we launched a dedicated service for the scoring of TLS in cancer patient biopsies.

    WordPress Lightbox