Immunotherapy of Colorectal Cancer

Jäger, Dirk; Halama, Niels; Zörnig, Inka; Klug, Paula; Krauß, Jürgen; Haag, Georg-Martin

doi:10.1159/000446713

Cited by 10 publications

(7 citation statements)

References 17 publications

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“…The current approaches to treat metastatic CRC (mCRC) involve multimodal therapy based on chemotherapy (including the combination of cytotoxic drugs) or targeted agents (such as bevacizumab, cetuximab, and panitumumab) (114). In the last few years, immunotherapy, which typically rely on the activation of T cells in the TME, has been considered for mCRC patients (115). Checkpoint inhibitors such as antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death protein (PD-1)/PD-1 ligand (PD-L1) resulted ineffective to produce durable clinical responses due to tumor-mediated immune evasion and resistance, caused by the presence, into the TME, of immunosuppressive cells like MDSCs (116).…”

Section: Mdscs In Colorectal Cancermentioning

confidence: 99%

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

2020

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Suppression of antitumor immune responses is one of the main mechanisms by which tumor cells escape from destruction by the immune system. Myeloid-derived suppressor cells (MDSCs) represent the main immunosuppressive cells present in the tumor microenvironment (TME) that sustain cancer progression. MDSCs are a heterogeneous group of immature myeloid cells with a potent activity against T-cell. Studies in mice have demonstrated that MDSCs accumulate in several types of cancer where they promote invasion, angiogenesis, and metastasis formation and inhibit antitumor immunity. In addition, different clinical studies have shown that MDSCs levels in the peripheral blood of cancer patients correlates with tumor burden, stage and with poor prognosis in multiple malignancies. Thus, MDSCs are the major obstacle to many cancer immunotherapies and their targeting may be a beneficial strategy for improvement the efficiency of immunotherapeutic interventions. However, the great heterogeneity of these cells makes their identification in human cancer very challenging. Since both the phenotype and mechanisms of action of MDSCs appear to be tumor-dependent, it is important to accurately characterized the precise MDSC subsets that have clinical relevance in each tumor environment to more efficiently target them. In this review we summarize the phenotype and the suppressive mechanisms of MDSCs populations expanded within different tumor contexts. Further, we discuss about their clinical relevance for cancer diagnosis and therapy.

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Section: Mdscs In Colorectal Cancermentioning

confidence: 99%

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

2020

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“…Also, immunotherapy quickly reached clinical application in melanoma, 2 while gastrointestinal cancer types are still lagging behind. 3 These shifts within the cancer immunotherapy field are highly relevant for clinicians, researchers and funding agencies. However, until now, these changes have not been quantified in a way that allows an unbiased assessment of past and possible future trends.…”

Section: Introductionmentioning

confidence: 99%

Large-scale database mining reveals hidden trends and future directions for cancer immunotherapy

et al. 2018

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Cancer immunotherapy has fundamentally changed the landscape of oncology in recent years and significant resources are invested into immunotherapy research. It is in the interests of researchers and clinicians to identify promising and less promising trends in this field in order to rationally allocate resources. This requires a quantitative large-scale analysis of cancer immunotherapy related databases.We developed a novel tool for text mining, statistical analysis and data visualization of scientific literature data. We used this tool to analyze 72002 cancer immunotherapy publications and 1469 clinical trials from public databases. All source codes are available under an open access license.The contribution of specific topics within the cancer immunotherapy field has markedly shifted over the years. We show that the focus is moving from cell-based therapy and vaccination towards checkpoint inhibitors, with these trends reaching statistical significance. Rapidly growing subfields include the combination of chemotherapy with checkpoint blockade. Translational studies have shifted from hematological and skin neoplasms to gastrointestinal and lung cancer and from tumor antigens and angiogenesis to tumor stroma and apoptosis.This work highlights the importance of unbiased large-scale database mining to assess trends in cancer research and cancer immunotherapy in particular. Researchers, clinicians and funding agencies should be aware of quantitative trends in the immunotherapy field, allocate resources to the most promising areas and find new approaches for currently immature topics.

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“…These results support a genetically-guided approach to immunotherapy in this unique subset. Currently, checkpoint inhibitors approved for different indications as well as novel checkpoint inhibitors (TIM-3, Lag-3, OX40, GITR, 4-1BB, CD40, CD70) are being studied in CRC (91). Recent work showed that MEK inhibition promotes infiltration of effector CD8 + T cells and synergize with a PD-L1 inhibitor in preclinical models (92).…”

Section: Crcmentioning

confidence: 99%

Personalized and precision medicine: integrating genomics into treatment decisions in gastrointestinal malignancies

Wang

Stenehjem

2017

J. Gastrointest. Oncol.

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The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in mutated metastatic colorectal cancer (mCRC). GI malignancies are clinically and molecularly heterogeneous. Unfortunately, development of biomarkers of response to therapy as well as targeted therapies for GI adenocarcinomas has fallen behind compared to other malignancies. Trastuzumab is the only FDA approved targeted therapy for GI adenocarcinomas for which a biomarker of response ( amplifications) is available. In addition, mutations are known to predict lack of response to epidermal growth factor receptor (EGFR) inhibitors in advanced colorectal cancer (CRC) patients. However, NGS has recently revealed that a number of actionable genetic aberrations are present at low prevalence across different GI malignancies. Prospective randomized clinical trials will determine whether matching actionable aberration with targeted therapy will contribute to improve survival in patients with GI malignancies. Here, we review current evidence for targeted therapies in GI malignancies, as well as application and pitfalls of NGS including tissue testing and liquid biopsies.

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Immunotherapy of Colorectal Cancer

Cited by 10 publications

References 17 publications

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

Large-scale database mining reveals hidden trends and future directions for cancer immunotherapy

Personalized and precision medicine: integrating genomics into treatment decisions in gastrointestinal malignancies

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