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

Wall, Isobelle; Boulat, Victoire; Shah, Aekta; Blenman, Kim; Wu, Yin; Alberts, Elena; Calado, Dinis Pedro; Salgado, Roberto; Grigoriadis, Anita

doi:10.3390/cancers14184505

Cited by 7 publications

(13 citation statements)

References 158 publications

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“…Such spatial characterization could also be extent to lymph nodes, given their increasingly importance in the context of breast cancer. 37 Our study has also clinical implications. Although anti-PD1 blockade prolongs the survival of TNBC patients, 38,39 a significant proportion of them does not benefit from immunotherapy.…”

Section: Discussionmentioning

confidence: 70%

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Clonal expansion of intra‐epithelial T cells in breast cancer revealed by spatial transcriptomics

Romanens

Chaskar

Marcone

et al. 2023

Intl Journal of Cancer

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The spatial distribution of tumor‐infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing tumors. Here, we present ST‐FFPE, a spatial transcriptomics method for the analysis of formalin‐fixed paraffin‐embedded samples, which opens the possibility of interrogating archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser‐capture, and can be used to study the cellular composition of tumor microenvironment. Focusing on triple‐negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra‐epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra‐epithelial T and B cells were consistently less diverse and more clonal than those of stromal T and B cells. T‐cell receptor (TCR) sequencing confirmed a reduced diversity and higher clonality of intra‐epithelial T cells relative to the corresponding stromal T cells. Analysis of the top 10 dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra‐epithelial T cells. Hyperexpanded clonotypes were more abundant among intra‐epithelial than stromal T cells. These findings validate the ST‐FFPE method and suggest an accumulation of antigen‐specific T cells within tumor core. Because ST‐FFPE is applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings.

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Section: Discussionmentioning

confidence: 70%

“…Considering the proven clinical importance of stromal TILs, 36 it may be envisaged that both compartments should be analyzed in order to understand the immune‐system of our patients. Such spatial characterization could also be extent to lymph nodes, given their increasingly importance in the context of breast cancer 37 …”

Section: Discussionmentioning

confidence: 99%

Clonal expansion of intra‐epithelial T cells in breast cancer revealed by spatial transcriptomics

Romanens

Chaskar

Marcone

et al. 2023

Intl Journal of Cancer

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“…Studies showed that some chemotherapeutic drugs appeared more effective in immuno-competent hosts than in immuno-deficient counterparts ( 20 ). These data suggested the fundamental role of global immune macroenvironment ( 17 , 24 , 25 ) as the basis for various therapies. Immunity is coordinated across diverse cell types and tissues.…”

Section: Introductionmentioning

confidence: 93%

Baseline splenic volume as a biomarker for clinical outcome and circulating lymphocyte count in gastric cancer

Zeng

Liu

et al. 2023

Front. Oncol.

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BackgroundThe spleen is the largest peripheral lymphoid organ in the body. Studies have implicated the spleen in the development of cancer. However, it is unknown whether splenic volume (SV) is associated with the clinical outcome of gastric cancer.MethodsData of gastric cancer patients treated with surgical resection were retrospectively analyzed. Patients were divided into three groups: underweight, normal-weight and overweight. Overall survival was compared in patients with high and low splenic volume. The correlation between splenic volume and peripheral immune cells were analyzed.ResultsOf 541 patients, 71.2% were male and the median age was 60. Underweight, normal-weight and overweight patients accounted for 5.4%, 62.3% and 32.3%, respectively. High splenic volume was associated with unfavorable prognosis across the three groups. In addition, the increase of splenic volume during neoadjuvant chemotherapy was not associated with prognosis. The baseline splenic volume was negatively correlated with lymphocytes (r=-0.21, p<0.001) and positively correlated with NLR (neutrophil-to-lymphocyte ratio) (r=0.24, p<0.001). In a group of patients (n=56), splenic volume was found to have negative correlation with CD4+T cells (r=-0.27, p=0.041) and NK cells (r=-0.30, p=0.025).ConclusionsThe presence of high splenic volume is a biomarker of unfavorable prognosis and reduced circulating lymphocytes in gastric cancer.

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“…23 In cancer, the antitumor responses become dysregulated and inefficient in the lymph nodes which serve as a primary site for antigen presentation and T-cell stimulation. 28 Hence, this study aims to explore the immune checkpoint molecule status and exhaustion-related facets of the CD8 + T cells found in the circulation and in the lymph nodes. Here, a subpopulation of CXCR5 + PD-1 + cytotoxic T cells was identified with high TIM-3, ICOS, and CD45RO expression in the lymph nodes from breast cancer patients but showed limited association with the clinical features of the patients.…”

Section: Introductionmentioning

confidence: 99%

“…In cancer, the antitumor responses become dysregulated and inefficient in the lymph nodes which serve as a primary site for antigen presentation and T‐cell stimulation 28 . Hence, this study aims to explore the immune checkpoint molecule status and exhaustion‐related facets of the CD8 + T cells found in the circulation and in the lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint status and exhaustion‐related phenotypes of CD8⁺ T cells from the tumor‐draining regional lymph nodes in breast cancer

Yilmaz,

Tavukcuoglu,

Horzum

et al. 2023

Cancer Medicine

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BackgroundFunctional status of T cells determines the responsiveness of cancer patients to immunotherapeutic interventions. Even though T cell‐mediated immunity is inaugurated in the tumor‐adjacent lymph nodes, peripheral blood has been routinely sampled for testing the immunological assays. The purpose of this study is to determine the immune checkpoint molecule expression and the exhaustion‐related phenotype of cytotoxic T cells in the regional lymph nodes from breast cancer patients.Patients and methodsMulticolor immunophenotyping was used to determine the expression of PD‐1, TIM‐3, LAG3, CTLA‐4, CCR7, CD45RO, CD127, CD25, CXCR5, and ICOS molecules on CD3+CD4−CD56−CD8+ cytotoxic T cells freshly obtained from the lymph nodes and the peripheral blood samples of the breast cancer patients. The results were assessed together with the clinical data.ResultsA population of cytotoxic T cells was noted with high PD‐1 and CXCR5 expression in the lymph nodes of the breast cancer patients. Co‐expression of PD‐1, CXCR5, TIM‐3, and ICOS indicated a follicular helper T cell (Tfh)‐like, exhaustion‐related immunophenotype in these cytotoxic T cells. Only a minor population with CTLA‐4 and LAG3 expression was noted. The PD‐1+CXCR5+ cytotoxic T cells largely displayed CD45RO+CCR7+ central memory markers. The amount of CXCR5‐expressing PD‐1− cytotoxic T cells was elevated in the lymph nodes of the patients.ConclusionThe regional lymph nodes of breast cancer patients harbor Tfh‐like exhausted cytotoxic T lymphocytes with high PD‐1 and TIM‐3 checkpoint molecule expression. The immunological conditions in the regional lymph nodes should be implicated for immune checkpoint immunotherapy (ICI) of cancer.

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

Cited by 7 publications

References 158 publications

Clonal expansion of intra‐epithelial T cells in breast cancer revealed by spatial transcriptomics

Clonal expansion of intra‐epithelial T cells in breast cancer revealed by spatial transcriptomics

Baseline splenic volume as a biomarker for clinical outcome and circulating lymphocyte count in gastric cancer

Immune checkpoint status and exhaustion‐related phenotypes of CD8⁺ T cells from the tumor‐draining regional lymph nodes in breast cancer

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

Cited by 7 publications

References 158 publications

Clonal expansion of intra‐epithelial T cells in breast cancer revealed by spatial transcriptomics

Clonal expansion of intra‐epithelial T cells in breast cancer revealed by spatial transcriptomics

Baseline splenic volume as a biomarker for clinical outcome and circulating lymphocyte count in gastric cancer

Immune checkpoint status and exhaustion‐related phenotypes of CD8+ T cells from the tumor‐draining regional lymph nodes in breast cancer

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Immune checkpoint status and exhaustion‐related phenotypes of CD8⁺ T cells from the tumor‐draining regional lymph nodes in breast cancer