Automated Quantification of Tertiary Lymphoid Structures in Human Tumor Samples Using Immunofluorescence and AI-Powered Analysis Pipeline.

The tumor microenvironment (TME) is a complex entity comprising not only tumor cells but also immune, stromal, and endothelial cells. Preclinical and clinical studies indicate that the density, localization, function, and organization of immune infiltration can influence survival probability and treatment response in many cancers. Among these cell organizations, the clustering of T and B cells into tertiary lymphoid structures (TLS) has been associated with favorable clinical outcomes.

Imaging Mass Cytometry to Decipher the Maturation of Tertiary Lymphoid Structures.

In the realm of inflammation, including conditions like cancers, infections, and autoimmune diseases, the emergence of tertiary lymphoid structures (TLS) holds significant implications for prognosis and treatment response. Yet, traditional methodologies such as immunohistochemistry and immunofluorescence falter in capturing the nuanced complexities of TLS, necessitating innovative approaches, like imaging mass cytometry (IMC), to unravel their significance. With the capacity to concurrently assess nearly 40 markers within the same tissue section, IMC transcends the constraints of traditional approaches.

Comparative Automated Quantification of Tertiary Lymphoid Structures in Two Distinct Mouse Models of Inflammation.

Tertiary lymphoid structures (TLS) have been reported to form within nonlymphoid tissues upon various inflammatory conditions, such as tumors or bacterial infections. In particular, the lungs of patients with NSCLC or bacterial infections (such as tuberculosis or aspergillosis) are the sites of TLS neogenesis. An increasing number of preclinical models have been used over the years to recapitulate as accurately as possible the mechanisms and kinetics of TLS formation that are continuously reported in the clinic.

Tertiary lymphoid structures in anticancer immunity.

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates where adaptive antitumour cellular and humoral responses can be elaborated. Initially described in non-small cell lung cancer as functional immune lymphoid structures associated with better clinical outcome, TLS have also been found in many other carcinomas, as well as melanomas and sarcomas, and associated with improved response to immunotherapy. The manipulation of TLS as a therapeutic strategy is now coming of age owing to the likely role of TLS in the improved survival of patients with cancer receiving immune checkpoint inhibitor treatment.

T follicular helper and B cell crosstalk in tertiary lymphoid structures and cancer immunotherapy.

Tumor-infiltrating lymphocytes (TILs) are critical in the elimination of cancer cells, a concept highlighted by recent advances in cancer immunotherapy. Significant evidence reveals that their organization in tertiary lymphoid structures together with specific subpopulation composition/balances stimulates cellular crosstalk and anti-tumor immunity in patients.

Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen.

Preclinical models and clinical studies have shown that anti-CD20-based treatment has multifaceted consequences on T-cell immunity. We have performed a prospective study of peripheral T-cell compartment in FL patients, all exhibiting high tumor burden and receiving rituximab-chemotherapy-based regimen (R-CHOP). Before treatment, FL patients harbor low amounts of peripheral naive T cells, but high levels of CD4 T, CD4 T and CD8 T subsets and significant amounts of CD38 HLA-DR activated T cells.