Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

Jacquelot, Nicolas; Tellier, Julie; Nutt, Stephen L.; Belz, Gabrielle T.

doi:10.1080/2162402x.2021.1900508

Cited by 78 publications

(37 citation statements)

References 158 publications

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“… 42 43 Although the predictive role of HEV in ICI has been less investigated, the tertiary lymphoid structure, which is an ectopic lymphoid structure with abundant HEV, was found to be a favorable biomarker for ICI therapy. 44 However, HEV was not always associated with the organized lymphoid structure and was often present within the loosely assembled lymphoid aggregates. 45 Moreover, HEV was a significant prognostic factor for RFS and OS in our study (data not shown), regardless of CLR, which resembles the tertiary lymphoid structure.…”

Section: Discussionmentioning

confidence: 99%

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

Park

Kim

et al. 2021

J Immunother Cancer

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BackgroundHigh endothelial venule (HEV) is a specialized vasculature for lymphocyte trafficking. While HEVs are frequently observed within gastric cancer (GC), the vascular–immune interaction between HEV and tumor-infiltrating lymphocytes (TILs) has not been well elucidated. In this study, we aimed to unveil the potential value of HEVs as a surrogate marker for T-cell inflamed immune microenvironment in GC using a large number of prospectively collected surgical specimens of GC.MethodsWe included 460 patients with GC who underwent surgical resection. Nanostring PanCancer immune profiling was performed to evaluate the immunological phenotype of GCs. HEV density and three distinct patterns of TILs (Crohn-like lymphoid reaction, peritumoral lymphoid reaction, and intratumoral lymphoid reaction) were analyzed for their relationship and evaluated as prognostic factors for relapse-free survival (RFS) and overall survival (OS).ResultsHEV-high GC revealed increased infiltration by immune cell subsets, including dendritic cells, CD8+ cytotoxic T cells, and CD4+ helper T cells. In addition, HEV-high GC demonstrated increased immune-modulating chemokines, type I or II interferon pathway, and immune checkpoints, all of which indicate the inflamed tumor microenvironment (TME). All three distinct patterns of TILs were associated with HEV density. In survival analysis, patients with HEV-high GC displayed significantly longer RFS and OS than those with HEV-low GC (p<0.001 for RFS, p<0.001 for OS). Multivariate analysis demonstrated that HEV was the most significant immunological prognostic factor for RFS (patients with high HEV compared with those with low HEV; HR 0.412, 95% CI 0.241 to 0.705, p=0.001) and OS (HR 0.547, 95% CI 0.329 to 0.909, p=0.02) after adjustment for age, stage, and TIL.ConclusionHEV is the most significant immunological prognosticator for RFS and OS in resected GC, indicating inflamed TME.

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Section: Discussionmentioning

confidence: 99%

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

Park

Kim

et al. 2021

J Immunother Cancer

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“… 25 TLS were defined as aggregates of lymphocytes with formation of a lymphoid based on hematoxylin and eosin stain and were counted with frequency/mm 2 . 26 …”

Section: Methodsmentioning

confidence: 99%

Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study

Sobottka

Nienhold

Nowak

et al. 2021

Journal of Immunotherapy

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“…NSCLC are often associated with the presence of 'Tertiary Lymphoid Structures' (TLS). TLS may occur at both the margins and the core of tumors, are spatially well-organized and are composed of T and B cell zones and germinal centers (51). Some authors have correlated the presence of B cells in TLS with favorable outcomes (52)(53)(54)(55)(56).…”

Section: Tertiary Lymphoid Structuresmentioning

confidence: 99%

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

et al. 2022

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In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of “classic” ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy.

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Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

Cited by 78 publications

References 158 publications

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study

Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade

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