New horizons in tumor microenvironment biology: challenges and opportunities

Chen, Fei; Zhuang, Xincun; Lin, Lilong; Yu, Pengfei; Wang, Ying; Shi, Yufang; Hu, Guohong; Sun, Yu

doi:10.1186/s12916-015-0278-7

Cited by 591 publications

(443 citation statements)

References 104 publications

(96 reference statements)

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“…[149] Emerging evidences suggest that the TME play a vital role in regulating tumorigenesis, including tumor intitation, development, proliferation and metastasis, and important response to cancer therapy. [150,151] TME is sought to be one of main drivers for the accumulation of nanoparticles/ nanomedicines in the tumor and highly heterogeneous TME contribute to the differential distribution of nanomedicines within tumor. In TME, the aberrant tumor vasculatures, elevated interstitial fluid pressure (IFP) and abnormalities in ECM are major hurdles in terms of effective penetration of the nanoparticles into the tumor tissue.…”

Section: Cancer Nanomedicines From the Tumor Biology Perspectivementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Section: Cancer Nanomedicines From the Tumor Biology Perspectivementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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“…По мере увеличения размеров опухолевого очага область влияния опухолевой ткани распространяется и на окружающую немалигнизированную ткань, которая приобретает сходство с самой опухолью по метаболическим особенностям и становится буфером между патологически измененной и здоровой тканью. При этом ткань перитуморальной зоны также не только подвергается влиянию опухоли, но и в свою очередь может влиять на дальнейшее её развитие [15][16][17].…”

Section: результаты и обсуждениеunclassified

The activity of redox-regulatory systems in the tumor and its surrounding tissues in various histological types of tumor

et al. 2016

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According to modern concepts cancer is a complex dynamic system having multiple relationships with both the immediate environment and with remote nonmalignant tissues and organs. Changes in the redox balance in them can result in disruption of the normal tissue control. Understanding of the biology of redox processes in a particular tumor and its surroundings, and of their functioning mechanisms is necessary for the development of new anti-cancer strategies based on the effects on the redox state of the tumor and surrounding tissue. Thus the aim of this work was to investigate activity of enzymatic systems influencing the redox state in the tumor tissue, peritumoral area and nonmalignant tissue (taken along the line of resection) for different histological types of tumors. The data obtained showed a similar level of reduced glutathione (GSH) in tumor tissues of gastric adenocarcinoma and vulvar squamous cell carcinoma, but its dynamics in the tissues surrounding the tumor was different. In contrast to the gastric adenocarcinoma the carcinoma of the vulva had a significant level of GSH and higher activity of glutathione dependent enzymes in the tumor tissue and its peritumoral area compared with the surrounding nonmalignant tissue. The results indicate that there are differences in the functioning of the redox regulatory systems in the tumor tissue and its surrounding tissues of various histological origin and localization, possibly due to different mechanisms involved in maintenance of the redox balance in the originally nonmalignant tissue

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“…These cells can recruit diversity of cell types, including endothelial cells, fibroblasts and immune cells, and, through production and secretion of stimulatory growth factors. This collection of cells and molecules together compose the tumor microenvironment [23]. We know the microenvironment plays a major role during the initiation and development of tumor progression.…”

Section: Immune Checkpointsmentioning

confidence: 99%

The Future of Checkpoint Blockade to Treat Cancer Patients

Scutti¹

2016

JCPCR

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The presence of several inhibitory pathways that block T cell responses -immune checkpoints, offers particular strategies for mobilizing the immune system to attack cancer cells. The best characterized of these immune checkpoints are CTLA-4 (Cytotoxic T lymphocyte associated protein 4) and PD-1 (Programmed cell death protein 1). CTLA-4 is expressed exclusively on CD4+ and CD8+ lymphocytes which restrains T cell proliferation by interfering with the interaction of CD28 with its ligands CD80 (B7-1) and CD86 (B7-2) on the surface of antigen presenting cells (APC's). PD-1 belongs to CD28 family and it is expressed on T cells, B cells, monocytes, Natural Killer (NK) and many tumor infiltrating lymphocytes (TIL's). Furthermore, PD-1 recruits a phosphatase and seems to inhibit with T cell antigen receptor mediated signaling. It has 2 ligands that have been described, PD-L1 and PD-L2, which are both expressed on dendritic cells and many tumors cells. Immunotherapeutic approaches to treat cancer patients have been evaluated during the last decades and today; immune checkpoints are the new paradigm for cancer treatment. The Food and Drug Administration (FDA) approved the antibody against CTLA-4 (Ipilimumab) in 2011 for the treatment of metastatic melanoma. To date, it is undergoing clinical trials for the treatment of non-small cell lung carcinoma (NSCLC), small cell lung cancer (SCLC), bladder and metastatic hormone refractory prostate cancer. Antibodies against PD-1 (Pembrolizumab and Nivolumab) were approved in 2014 by FDA for the treatment of melanoma patients that did not respond to prior treatment. This type of therapy symbolizes an innovative concept in cancer therapy due two ways: first, these drugs totally ignore the tumor cells -they reliant on the immune system and second, they are not used to activate the immune system against a particular cancer; they remove inhibitory molecules that block a successful antitumor T cell response.Antibodies to CTLA-4, PD-1 and PD-L1 have shown objective response against several cancer types in clinical trials with response rates of about 25%. This effect represents a special challenge for immunotherapy -since certain types of cancer have presented lower burden of mutation and higher immune regulatory molecules such as VISTA, TIM-3 and LAG-3. Here, I have raised recent advances in the understanding of the cancer immunotherapy mainly the role of blockade of immune checkpoints. Immunotherapy records a pivotal moment in cancer as long sought attempt to promote the immune system against tumors. The standard treatments for patients with several cancer types are in most cases, surgery, radiation and chemotherapy [3].Surgery offers a huge chance for a cure for many types of cancer, principally those that have not metastasis and diagnosed from the beginning. Radiotherapy is involved in many therapeutic treatments of cancer; however, severe side effects can occur months to years after treatment. Additionally, some cancer cells are strong enough to tolerate and retrieve from the d...

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New horizons in tumor microenvironment biology: challenges and opportunities

Cited by 591 publications

References 104 publications

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

The activity of redox-regulatory systems in the tumor and its surrounding tissues in various histological types of tumor

The Future of Checkpoint Blockade to Treat Cancer Patients

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