Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial

Voorwerk, Leonie; Slagter, Maarten; Horlings, Hugo M.; Sikorska, Karolina; Vijver, Koen K. Van de; Maaker, Michiel de; Nederlof, Iris; Kluin, Roelof J.C.; Warren, Sarah; Ong, SuFey; Wiersma, T.; Russell, Nicola S.; Lalezari, Ferry; Schouten, Philip C.; Bakker, Noor; Ketelaars, Steven L. C.; Peters, Dennis; Lange, Charlotte A.H.; Werkhoven, Erik van; Mandjes, Ingrid A.M.; Kemper, Inge; Onderwater, Suzanne; Chalabi, Myriam; Wilgenhof, Sofie; Haanen, John B.A.G.; Salgado, Roberto; Visser, Karin E. de; Sonke, Gabe S.; Wessels, Lodewyk; Linn, Sabine C.; Blank, Christian U.; Kok, Marleen

doi:10.1038/s41591-019-0520-5

Cited by 23 publications

(24 citation statements)

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“…TNBC is an aggressive subtype of breast cancer (accounting for 12-18%) (1). TNBC patients are often more likely to develop local recurrence and distant metastases than other types (2). As expected, patients with TNBC have worse clinical outcomes.…”

Section: Introductionmentioning

confidence: 86%

Unraveling Heterogeneity of Tumor Cells and Microenvironment and Its Clinical Implications for Triple Negative Breast Cancer

Jiang

Dong

et al. 2021

Front. Oncol.

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Objective: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, characterized by extensive intratumoral heterogeneity. We aimed to systematically characterize the tumor heterogeneity of TNBC.Methods: Single-cell RNA sequencing (scRNA-seq) of TNBC cells were obtained from the GSE118389 and GSE75688 datasets. After integration of the two datasets, cell clustering analysis was performed using the Seurat package. According to the marker genes of cell cycle, cell cycle of each cell cluster was determined. Then, function enrichment analysis of marker genes in each cell cluster was performed, followed by ligand–receptor signaling network analysis. CIBERSORT was used to estimate the proportion of 22 immune cells in each sample based on RNA-seq data of 58 normal adjacent tissues and 101 TNBC tissues. After that, prognostic value of immune cells was assessed.Results: In the integrated datasets, five cells types including B cells, myeloid cells, stromal cells, T cells, and tumor cells were clustered. Functional enrichment analysis revealed the functional heterogeneity of genes in each cell. Intercellular communication networks were conducted based on ligand–receptor pairs. The heterogeneity in the fractions of 22 immune cells was found in TNBC tissues. Furthermore, there was a significant difference in the fractions of these immune cells between adjacent normal tissues and TNBC tissues. Among them, M2 macrophages and neutrophils were significantly associated with clinical outcomes of TNBC. Moreover, the fractions of T cells CD4 memory resting, monocytes, neutrophils, M1 macrophages, and T cells CD4 memory activated were significantly correlated with clinical characteristics of TNBC. As shown in PCA results, these immune cells could significantly distinguish TNBC tissues into adjacent normal tissues.Conclusion: Our findings characterized the tumor heterogeneity of TNBC, which deepened the understanding of the complex interactions between tumor cells and their microenvironment, especially immune cells.

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Section: Introductionmentioning

confidence: 86%

Unraveling Heterogeneity of Tumor Cells and Microenvironment and Its Clinical Implications for Triple Negative Breast Cancer

Jiang

Dong

et al. 2021

Front. Oncol.

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“…Monoclonal antibodies against PD-1/PD-L1 and CTLA-4 have emerged as powerful tools to release the inhibitory regulation of T cell activation (114,115). To date, multiple blocking monoclonal antibodies have been approved by the US Food and Drug Administration (FDA) including the anti CTLA-4 antibody ipilimumab, anti-PD1 antibodies pembrolizumab, nivolumab and cemiplimab and anti-PD-L1 antibodies atezolizumab, avelumab and durvalumab (116,117). Treatment response to immune checkpoint inhibitors varies greatly with only a small proportion of patients experiencing better survival rates (118,119).…”

Section: Immune Checkpoint Inhibition In Triple Negative Breast Cancermentioning

confidence: 99%

“…The phase 2 TONIC trial (NCT02499367) evaluated the efficacy of PD1 blockade with nivolumab in pretreated mTNBC (cyclophosphamide, cisplatin, doxorubicin). Of note, nivolumab therapy preceded by doxorubicin resulted in an ORR of 35 compared to 23% for cisplatin and 17% for patients without preceding chemotherapy, suggesting that pretreatment with chemotherapy can induce an inflamed tumor microenvironment (117). In comparison with metastatic TNBC, significant more studies have been conducted in locally advanced or early stage TNBC.…”

Section: Pd1/pd-l1 Antibody-chemotherapy Combination Treatmentmentioning

confidence: 99%

“…Two emerging predictive biomarkers are the number of tumor infiltrating lymphocytes and the tumor mutational burden. Increased number of TILs have been associated with better overall survival in TNBC patients treated with ICI monotherapy or in combination with chemotherapy (117,136). The relative importance of intratumoral TILs (iTILs) versus stromal TILs (sTILs) has not clearly been defined yet and might differ between tumor types.…”

Section: Predictive Biomarkers In Immune Checkpoint Inhibitionmentioning

confidence: 99%

“…In breast cancer, both iTILs and sTILs have been correlated with clinical outcome and chemotherapy response (59,60,63,78,169). Moreover, in metastatic TNBC sTILs have been correlated with treatment response to pembrolizumab, atezolizumab, and nivolumab (117,124). Thus, the International Immuno-Oncology Biomarker Working Group published guidelines for the assessment of stromal and intra-tumoral TILs in a wide range of solid tumor types (170).…”

Section: Predictive Biomarkers In Immune Checkpoint Inhibitionmentioning

confidence: 99%

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Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects

2021

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Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient’s own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.

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Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer

Zhang,

Cai,

Yan

2023

J Cancer Res Clin Oncol

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Background Immunotherapy has shown promise in the treatment of esophageal cancer, but using it alone only benefits a small number of patients. Most patients either do not have a significant response or develop secondary drug resistance. The combination of radiotherapy and immunotherapy appears to be a promising approach to treating esophageal cancer. Purpose We reviewed milestone clinical trials of radiotherapy combined with immunotherapy for esophageal cancer. We then discussed potential biomarkers for radiotherapy combined with immunotherapy, including programmed cell death-ligand 1 (PD-L1) status, tumor mutation burden (TMB), tumor-infiltrating lymphocytes, ct-DNA, imaging biomarkers, and clinical factors. Furthermore, we emphasize the key mechanisms of radiation therapy-induced immune stimulation and immune suppression in order to propose strategies for overcoming immune resistance in radiation therapy (RT). Lastly, we discussed the emerging role of low-dose radiotherapy (LDRT) , which has become a promising approach to overcome the limitations of high-dose radiotherapy. Conclusion Radiotherapy can be considered a triggering factor for systemic anti-tumor immune response and, with the assistance of immunotherapy, can serve as a systemic treatment option and potentially become the standard treatment for cancer patients.

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Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial

Cited by 23 publications

References 0 publications

Unraveling Heterogeneity of Tumor Cells and Microenvironment and Its Clinical Implications for Triple Negative Breast Cancer

Unraveling Heterogeneity of Tumor Cells and Microenvironment and Its Clinical Implications for Triple Negative Breast Cancer

Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects

Opportunities and challenges in combining immunotherapy and radiotherapy in esophageal cancer

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