Immune analysis of lymph nodes in relation to the presence or absence of tumor infiltrating lymphocytes in triple-negative breast cancer

Quintana, Ángela; Peg, Vicente; Prat, Aleix; Moliné, Teresa; Villacampa, Guillermo; Paré, Laia; Galván, Patricia; Dientsmann, Rodrigo; Schmid, Peter; Curigliano, Giuseppe; Muñoz‐Couselo, Eva; Peréz-García, José Manuel; Blanco-Heredia, Juan; Anjos, Carla dos; Vázquez, Miguél; Mattos-Arruda, Leticia De; Cortés, Javier

doi:10.1016/j.ejca.2021.01.037

Cited by 16 publications

(15 citation statements)

References 31 publications

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“…Within an individual tumor, heterogeneity occurs at the level of the genome, transcriptome and proteome, which leads to the diversity of cell populations and tissue morphology [3,9,14,15]. As an example, recent studies have shown that tumor-infiltrating lymphocytes (TILs) in the primary tumor play an important role in therapy response and prognosis in breast cancer [4,[16][17][18][19][20][21][22][23][24][25][26]]. Yet, improved clinical outcomes were associated with the presence of TILs in some but not all tumor types and in some but not all patients [4,[27][28][29][30].…”

Section: Introduction 1biology and Prognostic Biomarkers In Breast Cancermentioning

confidence: 99%

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler

Bergholtz

Carter

Cesano

et al. 2021

Cancers

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Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity.

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Section: Introduction 1biology and Prognostic Biomarkers In Breast Cancermentioning

confidence: 99%

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler

Bergholtz

Carter

Cesano

et al. 2021

Cancers

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“…TNBC patients with stromal TIL levels higher than 20% have more germinal centres in their cancer-free LNs, while the identification of TLSs in the TME correlates with an increased number of germinal centres in metastatic LNs [ 50 ]. In alignment with this, Quintana et al studied similar features in a LN-negative TNBC cohort and found that TNBC patients with >50% TILs have more and larger germinal centres in their LNs and more TLSs at their primary tumour site compared to patients with <5% TILs [ 57 ]. We, too, have evidenced immune activation via the formation of germinal centres in LNs in level 1 of the axilla (closest to the primary tumour), as compared to level 3 LNs (most distal to the primary carcinoma) which do not show any germinal centre formation [ 54 ].…”

Section: Lymph Nodes: the Immune Capital Of Anti-tumour Responses In ...mentioning

confidence: 88%

“…In murine models, the exhausted T cell compartment in the TME can be replenished with a pool of stem-like Tcf7+ effector CD8+ T cells from the tumour-draining LN [ 94 ]. In humans, breast cancer patients with low TIL levels (<5%) at their primary tumour express higher levels of immune checkpoint molecules, including CTLA-4 and OX-40, in their tumour-draining LNs than patients with high TIL levels (>50%) [ 57 ], leading to the conjecture that the tumour-draining LN is one source of TILs and that T cell deactivation in the tumour-draining LN may contribute to a dampened immune response at the primary tumour site. TCR sequencing of the primary tumour and tumour-draining LN T cells revealed extensive clonotype overlap between expanded CD8+ T cells from both sites.…”

Section: Lymph Nodes: the Immune Capital Of Anti-tumour Responses In ...mentioning

confidence: 99%

Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

Wall

Boulat

Shah

et al. 2022

Cancers

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During the anti-tumour response to breast cancer, the primary tumour, the peripheral blood, and the lymph nodes each play unique roles. Immunological features at each site reveal evidence of continuous immune cross-talk between them before, during and after treatment. As such, immune responses to breast cancer are found to be highly dynamic and truly systemic, integrating three distinct immune sites, complex cell-migration highways, as well as the temporal dimension of disease progression and treatment. In this review, we provide a connective summary of the dynamic immune environment triad of breast cancer. It is critical that future studies seek to establish dynamic immune profiles, constituting multiple sites, that capture the systemic immune response to breast cancer and define patient-selection parameters resulting in more significant overall responses and survival rates for breast cancer patients.

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“…The immune system plays a key role in cancer, but differences between individuals can lead to different outcomes. A high number of tumor-infiltrating lymphocytes (TIL) in triple-negative breast cancer (TNBC) are related to a better prognosis ( 1 ), although not in all patients ( 2 ). Several factors influence a good antitumoral immune response, such as the recognition of neoantigens, the presence of immunomodulatory mediators, or the cellular composition and diversity of TIL, including the presence of antigen-presenting cells (APC) such as dendritic cells (DC) or B cells.…”

Section: Introductionmentioning

confidence: 99%

Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report

et al. 2021

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EBV-specific T cells have been recently described to be involved in fatal encephalitis and myocarditis in cancer patients after immune checkpoint therapies. Here, we report the study of a human triple-negative breast cancer tumor (TNBC) and EBV-transformed B cells obtained from a patient-derived xenograft (PDX) that progressed into a lymphocytic neoplasm named xenograft-associated B-cell lymphoma (XABCL). T-cell receptor (TCR) high-throughput sequencing was performed to monitor the T-cell clonotypes present in the different samples. Forty-three T-cell clonotypes were found infiltrating the XABCL tissue after three passes in mice along 6 months. Eighteen of these (42%) were also found in the TNBC biopsy. TCR infiltrating the XABCL tissue showed a very restricted T-cell repertoire as compared with the biopsy-infiltrating T cells. Consequently, T cells derived from the TNBC biopsy were expanded in the presence of the B-cell line obtained from the XABCL (XABCL-LCL), after which the TCR repertoire obtained was again very restricted, i.e., only certain clonotypes were selected by the B cells. A number of these TCRs had previously been reported as sequences involved in infection, cancer, and/or autoimmunity. We then analyzed the immunopeptidome from the XABCL-LCL, to identify putative B-cell-associated peptides that might have been expanding these T cells. The HLA class I and class II-associated peptides from XABCL-LCL were then compared with published repertoires from LCL of different HLA typing. Proteins from the antigen processing and presentation pathway remained significantly enriched in the XABCL-LCL repertoire. Interestingly, some class II-presented peptides were derived from cancer-related proteins. These results suggest that bystander tumor-infiltrating EBV+ B cells acting as APC may be able to interact with tumor-infiltrating T cells and influence the TCR repertoire in the tumor site.

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Immune analysis of lymph nodes in relation to the presence or absence of tumor infiltrating lymphocytes in triple-negative breast cancer

Cited by 16 publications

References 31 publications

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler

Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report

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