Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

Takeuchi, Shintaro; Baghdadi, Muhammad; Tsuchikawa, Takahiro; Wada, Haruka; Nakamura, Tõru; Abe, Hiroki; Nakanishi, Sayaka; Usui, Yuu; Higuchi, Kohtaro; Takahashi, Mitsuru; Inoko, Kazuho; Sato, Syoki; Takano, Hironobu; Shichinohe, Toshiaki; Seino, Ken‐ichiro; Hirano, Satoshi

doi:10.1158/0008-5472.can-14-2921

Cited by 129 publications

(102 citation statements)

References 51 publications

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“…In mouse model studies, paclitaxel and doxorubicin treatments have been reported to increase the recruitment of TAMs in PyMT-MMTV mammary carcinoma, which then induces the treatment resistance [87,88]. Similarly, gemcitabine treatment recruits more TAMs into TME with immune suppressive functions in mouse pancreatic cancer model [89]. It has also been shown recently that chemotherapy agents, such as paclitaxel and cisplatin, remodel TME by inducing Jagged1 expression in osteoblasts and mesenchymal stem cells, which feeds back to tumor cells to activate Notch signaling and promotes chemo-resistance [90].…”

Section: Chemo-and Radiotherapiesmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

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Section: Chemo-and Radiotherapiesmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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“…NSG or NRG mice that lack B and T cells as well as interleukin 2 receptor gamma) 55–57 . These host deficiencies substantially increase the engraftment rate at the expense of functional immunity, which is an important consideration in defining response to therapy 3,4,58 . To address this shortcoming, co-engraftment of the patient’s hematopoietic stem cells can reconstitute a more relevant immune contexture and perhaps more accurately model the disease 59–63 .…”

Section: Pancreas Cancer Modelsmentioning

confidence: 99%

Understanding Disease Biology and Informing the Management of Pancreas Cancer With Preclinical Model Systems

Whittle¹,

Hingorani²

2017

Cancer J

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Recent advances in cytotoxic therapies for pancreatic ductal adenocarcinoma (PDA) are overshadowed by stalled clinical progress of more targeted strategies, the vast majority of which have failed in clinical trials. Inability to translate preclinical promise into clinical efficacy derives, in part, from imperfect disease modeling and mismatches between preclinical and clinical study design and execution. Into these gaps fall our patients who enter the clinical trial landscape expectantly and bear the brunt of its inadequacies. If improving patient survival is paramount, then it must be acknowledged that the failure of a Phase 3 trial represents a larger failure of all of the work that preceded it. Repeated failures suggest a need to reappraise the current preclinical-to-clinical apparatus. Exceptional models of PDA are now available to researchers and the first steps toward a new era of success can begin with improved selection and application of these systems. Herein we discuss the key features of the major preclinical platforms for PDA and propose a paradigm for rigorous interrogation of prospective therapies.

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“…Another possibility is that the tumor-infiltrating T cells are kept at bay by co-infiltrating suppressive myeloid cells, present in great numbers in ovarian cancer and PDA (41)(42)(43)(44). It is still unclear how all the effects of the tumor microenvironment act in concert on the adaptive immune response to tumors, and therefore much work is yet to be done.…”

Section: Cautionary Tails: Limitations Of Mouse Models In Predicting mentioning

confidence: 99%

De-Risking Immunotherapy: Report of a Consensus Workshop of the Cancer Immunotherapy Consortium of the Cancer Research Institute

Mellman¹,

Hubbard-Lucey

Tontonoz

et al. 2016

Cancer Immunology Research

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With the recent FDA approvals of pembrolizumab and nivolumab, and a host of additional immunomodulatory agents entering clinical development each year, the field of cancer immunotherapy is changing rapidly. Strategies that can assist researchers in choosing the most promising drugs and drug combinations to move forward through clinical development are badly needed in order to reduce the likelihood of late-stage clinical trial failures. On October 5, 2014, the Cancer Immunotherapy Consortium of the Cancer Research Institute, a collaborative think tank composed of stakeholders from academia, industry, regulatory agencies, and patient interest groups, met to discuss strategies for de-risking immunotherapy development, with a focus on integrating preclinical and clinical studies, and conducting smarter early-phase trials, particularly for combination therapies. Several recommendations were made, including making better use of clinical data to inform preclinical research, obtaining adequate tissues for biomarker studies, and choosing appropriate clinical trial endpoints to identify promising drug candidates and combinations in nonrandomized early-phase trials.

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Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. PDAC builds a tumor microenvironment that plays critical roles in tumor progression and metastasis.

Cited by 129 publications

References 51 publications

Complex interplay between tumor microenvironment and cancer therapy

Complex interplay between tumor microenvironment and cancer therapy

Understanding Disease Biology and Informing the Management of Pancreas Cancer With Preclinical Model Systems

De-Risking Immunotherapy: Report of a Consensus Workshop of the Cancer Immunotherapy Consortium of the Cancer Research Institute

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