Immunotherapy for early breast cancer: too soon, too superficial, or just right?

Franzoi, Maria Alice; Romano, Emanuela; Piccart, Martine

doi:10.1016/j.annonc.2020.11.022

Cited by 93 publications

(79 citation statements)

References 98 publications

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“…Triple-negative breast cancer (TNBC) is the most malignant and aggressive subtype of breast cancer, which is pathologically featured by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression (1)(2)(3). Despite its clinical characteristics of high invasion, metastasis, a high rate of early relapse, a dismal prognosis, and a limited response to conventional chemotherapies or targeted therapies, immunotherapy are showing great promise and its use has been approved in combination with traditional treatment options in TNBC (2,(4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

High Throughput Transcriptome Data Analysis and Computational Verification Reveal Immunotherapy Biomarkers of Compound Kushen Injection for Treating Triple-Negative Breast Cancer

Liu

Zhang³

et al. 2021

Front. Oncol.

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BackgroundAlthough notable therapeutic and prognostic benefits of compound kushen injection (CKI) have been found when it was used alone or in combination with chemotherapy or radiotherapy for triple-negative breast cancer (TNBC) treatment, the effects of CKI on TNBC microenvironment remain largely unclear. This study aims to construct and validate a predictive immunotherapy signature of CKI on TNBC.MethodsThe UPLC-Q-TOF-MS technology was firstly used to investigate major constituents of CKI. RNA sequencing data of CKI-perturbed TNBC cells were analyzed to detect differential expression genes (DEGs), and the GSVA algorithm was applied to explore significantly changed pathways regulated by CKI. Additionally, the ssGSEA algorithm was used to quantify immune cell abundance in TNBC patients, and these patients were classified into distinct immune infiltration subgroups by unsupervised clustering. Then, prognosis-related genes were screened from DEGs among these subgroups and were further overlapped with the DEGs regulated by CKI. Finally, a predictive immunotherapy signature of CKI on TNBC was constructed based on the LASSO regression algorithm to predict mortality risks of TNBC patients, and the signature was also validated in another TNBC cohort.ResultsTwenty-three chemical components in CKI were identified by UPLC-Q-TOF-MS analysis. A total of 3692 DEGs were detected in CKI-treated versus control groups, and CKI significantly activated biological processes associated with activation of T, natural killer and natural killer T cells. Three immune cell infiltration subgroups with 1593 DEGs were identified in TNBC patients. Then, two genes that can be down-regulated by CKI with hazard ratio (HR) > 1 and 26 genes that can be up-regulated by CKI with HR < 1 were selected as key immune- and prognosis-related genes regulated by CKI. Lastly, a five-gene prognostic signature comprising two risky genes (MARVELD2 and DYNC2I2) that can be down-regulated by CKI and three protective genes (RASSF2, FERMT3 and RASSF5) that can be up-regulated by CKI was developed, and it showed a good performance in both training and test sets.ConclusionsThis study proposes a predictive immunotherapy signature of CKI on TNBC, which would provide more evidence for survival prediction and treatment guidance in TNBC as well as a paradigm for exploring immunotherapy biomarkers in compound medicines.

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Section: Introductionmentioning

confidence: 99%

High Throughput Transcriptome Data Analysis and Computational Verification Reveal Immunotherapy Biomarkers of Compound Kushen Injection for Treating Triple-Negative Breast Cancer

Liu

Zhang³

et al. 2021

Front. Oncol.

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“…Recently, immunotherapy has been approved for different cancers, such as melanoma, prostate cancer, lymphoma, renal cell carcinoma, and breast cancer (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). The most successful of these strategies involve immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the Transcriptome Profile Reveals the Potential Roles Played by Long Noncoding RNAs in Immunotherapy for Sarcoma

Pang

Hao

2021

Front. Oncol.

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BackgroundLong-term survival is still low for high-risk patients with soft tissue sarcoma treated with standard management options, including surgery, radiation, and chemotherapy. Immunotherapy is a promising new potential treatment paradigm. However, the application of immune checkpoint inhibitors for the treatment of patients with sarcoma did not yield promising results in a clinical trial. Therefore, there is a considerable need to identify factors that may lead to immune checkpoint inhibitor resistance.MethodsIn this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) to detect key long noncoding RNAs (lncRNAs) that were correlated with immune checkpoint inhibitory molecules in sarcoma. The expression levels of these lncRNAs and their correlation with patient prognosis were explored. The upstream long noncoding RNAs were also examined via 450K array data from the TCGA. The potential roles of these lncRNAs were further examined via KEGG and GO analysis using DAVID online software. Finally, the relationship between these lncRNAs and immune cell infiltration in tumors and their effect on immune checkpoint inhibitors were further explored.ResultsWe identified lncRNAs correlated with tumor cell immune evasion in sarcoma. The expression of these lncRNAs was upregulated and correlated with worse prognosis in sarcoma and other human cancer types. Moreover, low DNA methylation occupation of these lncRNA loci was detected. Negative correlations between DNA methylation and lncRNA expression were also found in sarcoma and other human cancer types. KEGG and GO analyses indicated that these lncRNAs correlated with immune evasion and negative regulation of the immune response in sarcoma. Finally, high expression of these lncRNAs correlated with more suppressive immune cell infiltration and reduced sensitivity to immune checkpoint inhibitors in sarcoma and other human cancer types.ConclusionOur results suggest that long noncoding RNAs confer immune checkpoint inhibitor resistance in human cancer. Further characterization of these lncRNAs may help to elucidate the mechanisms underlying immune checkpoint inhibitor resistance and uncover a novel therapeutic intervention point for immunotherapy.

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“…The most significant predictors of immunotherapy response include the PD-L1 status, tumour mutational burden (TMB), immune gene signatures, and the abundance of tumour infiltrating lymphocytes (TILs) [15][16][17]. In line with this, the majority of pancreatic ductal adenocarcinomas have poor immune cell infiltration [18] and the absence of a response in pancreatic cancer patients is thought to be due to the highly immunosuppressive TME which harbours a higher proportion of tumour-associated macrophages (TAMs), regulatory CD4+ T cells (T regs ), myeloid-derived suppressor cells (MDSCs), in addition to the development of a dense desmoplastic stroma that is thought to be a physical barrier to immune infiltration [19].…”

Section: Introduction 1the Advancement and Efficacy Of Immunotherapies Give Hopementioning

confidence: 99%

Improved Immunotherapy Efficacy by Vascular Modulation

Newport

Pedrosa

Njegic

et al. 2021

Cancers

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Several strategies have been developed to modulate the tumour vasculature for cancer therapy including anti-angiogenesis and vascular normalisation. Vasculature modulation results in changes to the tumour microenvironment including oxygenation and immune cell infiltration, therefore lending itself to combination with cancer therapy. The development of immunotherapies has led to significant improvements in cancer treatment. Particularly promising are immune checkpoint blockade and CAR T cell therapies, which use antibodies against negative regulators of T cell activation and T cells reprogrammed to better target tumour antigens, respectively. However, while immunotherapy is successful in some patients, including those with advanced or metastatic cancers, only a subset of patients respond. Therefore, better predictors of patient response and methods to overcome resistance warrant investigation. Poor, or periphery-limited, T cell infiltration in the tumour is associated with poor responses to immunotherapy. Given that (1) lymphocyte recruitment requires leucocyte–endothelial cell adhesion and (2) the vasculature controls tumour oxygenation and plays a pivotal role in T cell infiltration and activation, vessel targeting strategies including anti-angiogenesis and vascular normalisation in combination with immunotherapy are providing possible new strategies to enhance therapy. Here, we review the progress of vessel modulation in enhancing immunotherapy efficacy.

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Immunotherapy for early breast cancer: too soon, too superficial, or just right?

Cited by 93 publications

References 98 publications

High Throughput Transcriptome Data Analysis and Computational Verification Reveal Immunotherapy Biomarkers of Compound Kushen Injection for Treating Triple-Negative Breast Cancer

High Throughput Transcriptome Data Analysis and Computational Verification Reveal Immunotherapy Biomarkers of Compound Kushen Injection for Treating Triple-Negative Breast Cancer

Integrated Analysis of the Transcriptome Profile Reveals the Potential Roles Played by Long Noncoding RNAs in Immunotherapy for Sarcoma

Improved Immunotherapy Efficacy by Vascular Modulation

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