scholarly journals Nanoparticle-Based Therapies for Turning Cold Tumors Hot: How to Treat an Immunosuppressive Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Giulio Giustarini ◽  
Andrea Pavesi ◽  
Giulia Adriani
Keyword(s):  
Therapeutic Strategies ◽  
Effector T Cells ◽  
Inorganic Nanoparticles ◽  
Tumor Infiltration ◽  
Patient Stratification ◽  
Immune Microenvironment ◽  
Primary Parameter ◽  
Tumor Immune Microenvironment ◽  
Immunosuppressive Tumor Microenvironment ◽  
Novel Therapeutic Strategies

Nanotechnologies are rapidly increasing their role in immuno-oncology in line with the need for novel therapeutic strategies to treat patients unresponsive to chemotherapies and immunotherapies. The tumor immune microenvironment (TIME) has emerged as critical for tumor classification and patient stratification to design better treatments. Notably, the tumor infiltration of effector T cells plays a crucial role in antitumor responses and has been identified as the primary parameter to define hot, immunosuppressed, excluded, and cold tumors. Organic and inorganic nanoparticles (NPs) have been applied as carriers of new targeted therapies to turn cold or altered (i.e., immunosuppressed or excluded) tumors into more therapeutically responsive hot tumors. This mini-review discusses the significant advances in NP-based approaches to turn immunologically cold tumors into hot ones.

scholarly journals Tumor-Associated Macrophages: Critical Players in Drug Resistance of Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Maoyu Xiao ◽  
Jun He ◽  
Liyang Yin ◽  
Xiguan Chen ◽  
Xuyu Zu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Potential Possibility ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies

Drug resistance is one of the most critical challenges in breast cancer (BC) treatment. The occurrence and development of drug resistance are closely related to the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs), the most important immune cells in TIME, are essential for drug resistance in BC treatment. In this article, we summarize the effects of TAMs on the resistance of various drugs in endocrine therapy, chemotherapy, targeted therapy, and immunotherapy, and their underlying mechanisms. Based on the current overview of the key role of TAMs in drug resistance, we discuss the potential possibility for targeting TAMs to reduce drug resistance in BC treatment, By inhibiting the recruitment of TAMs, depleting the number of TAMs, regulating the polarization of TAMs and enhancing the phagocytosis of TAMs. Evidences in our review support it is important to develop novel therapeutic strategies to target TAMs in BC to overcome the treatment of resistance.

scholarly journals The effect of PEGylation on the efficacy and uptake of an immunostimulatory nanoparticle in the tumor immune microenvironment

2021 ◽  
Author(s):  
Wyatt M. Becicka ◽  
Peter Bielecki ◽  
Morgan Lorkowski ◽  
Taylor J. Moon ◽  
Yahan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Immunosuppressive Tumor Microenvironment

The efficacy of immunotherapies is often limited by the immunosuppressive tumor microenvironment, which is populated with dysfunctional innate immune cells. To reprogram the tumor-resident innate immune cells, we developed an...

scholarly journals Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

2020 ◽  
Vol 217 (8) ◽  
Author(s):  
Ali Hussain ◽  
Veronique Voisin ◽  
Stephanie Poon ◽  
Christina Karamboulas ◽  
Ngoc Hoang Bao Bui ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Cancer Progression ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Cancer Associated Fibroblasts ◽  
Patient Stratification ◽  
Functional States ◽  
Novel Therapeutic Strategies ◽  
First Time

Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes, the roles they play in cancer progression, and molecular mediators of the CAF “state.” Here, we identify a novel cell surface pan-CAF marker, CD49e, and demonstrate that two distinct CAF states, distinguished by expression of fibroblast activation protein (FAP), coexist within the CD49e+ CAF compartment in high-grade serous ovarian cancers. We show for the first time that CAF state influences patient outcomes and that this is mediated by the ability of FAP-high, but not FAP-low, CAFs to aggressively promote proliferation, invasion and therapy resistance of cancer cells. Overexpression of the FAP-low–specific transcription factor TCF21 in FAP-high CAFs decreases their ability to promote invasion, chemoresistance, and in vivo tumor growth, indicating that it acts as a master regulator of the CAF state. Understanding CAF states in more detail could lead to better patient stratification and novel therapeutic strategies.

scholarly journals Recent Advancements in Nanomedicine for ‘Cold’ Tumor Immunotherapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Qinjun Chen ◽  
Tao Sun ◽  
Chen Jiang
Keyword(s):  
Time Reversal ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Clinical Success Rate ◽  
Therapeutic Strategies ◽  
Immune Microenvironment ◽  
T Cell Infiltration ◽  
Tumor Immune Microenvironment ◽  
Anticancer Immunotherapy

AbstractAlthough current anticancer immunotherapies using immune checkpoint inhibitors (ICIs) have been reported with a high clinical success rate, numerous patients still bear ‘cold’ tumors with insufficient T cell infiltration and low immunogenicity, responding poorly to ICI therapy. Considering the advancements in precision medicine, in-depth mechanism studies on the tumor immune microenvironment (TIME) among cold tumors are required to improve the treatment for these patients. Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy, activates immune function, modulates the TIME, and has been applied in combination with other anticancer therapeutic strategies. This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies, as well as a brief talk about the feasibility of clinical translation.

NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy

2020 ◽  
Author(s):  
zhihong sun ◽  
Guanjun Deng ◽  
Xinghua Peng ◽  
Xiuli Xu ◽  
Lanlan Liu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Photothermal Therapy ◽  
Whole Body ◽  
Mature Dendritic Cell ◽  
Immune Microenvironment ◽  
Highly Efficient ◽  
Tumor Immune Microenvironment ◽  
Shock Proteins ◽  
Mild Temperature ◽  
Broad Interest

Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination.

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