bims-stacyt 2020-05-31 papers

Cancer Lett. 2020 May 26. pii: S0304-3835(20)30269-X. [Epub ahead of print]

Hypoxia: Turning vessels into vassals of cancer immunotolerance.

Hypoxia is a universal feature of solid cancers caused by a mismatch between cellular oxygen supply and consumption. To meet the increased demand for oxygen, hypoxic cancer cells (CCs) induce a multifaceted process known as angiogenesis, wherein new vessels are formed by the sprouting of pre-existing ones. In addition to providing oxygen for growth and an exit route for dissemination, angiogenic vessels and factors are co-opted by CCs to enable the generation of an immunotolerant, hypoxic tumor microenvironment, leading to therapeutic failure and mortality. In this review, we discuss how hypoxia-inducible factors (HIFs), the mechanistic target of rapamycin (mTOR), and the unfolded protein response (UPR) control angiogenic factors serving both vascular and immunomodulatory functions in the tumor microenvironment. Possible therapeutic strategies, wherein targeting oxygen sensing might enhance anti-angiogenic and immunologically-mediated anti-cancer responses, are suggested.

Keywords: Angiogenesis; Cancer; HIF; Hypoxia; Hypoxia-inducible factors; Immunotherapy; Oxygen sensing; Targeted therapy; Tumor microenvironment; UPR; mTOR

DOI: https://doi.org/10.1016/j.canlet.2020.05.015

Trends Cancer. 2020 Jun;pii: S2405-8033(20)30081-9. [Epub ahead of print]6(6): 489-505

Tumour Cell Secretome in Chemoresistance and Tumour Recurrence.

Emma C Madden, Adrienne M Gorman, Susan E Logue, Afshin Samali.

Chemoresistance is a major factor driving tumour relapse and the high rates of cancer-related deaths. Understanding how cancer cells overcome chemotherapy-induced cell death is critical in promoting patient survival. One emerging mechanism of chemoresistance is the tumour cell secretome (TCS), an array of protumorigenic factors released by tumour cells. Chemotherapy exposure can also alter the composition of the TCS, known as therapy-induced TCS, and can promote tumour relapse and the formation of an immunosuppressive tumour microenvironment (TME). Here, we outline how the TCS can protect cancer cells from chemotherapy-induced cell death. We also highlight recent evidence describing how therapy-induced TCS can impact cancer stem cell (CSC) expansion and tumour-associated immune cells to enable tumour regrowth and antitumour immunity.

Keywords: cancer stem cells (CSCs); chemoresistance; immune escape, tumour cell secretome (TCS); tumour microenvironment (TME); tumour relapse

DOI: https://doi.org/10.1016/j.trecan.2020.02.020

Cell Immunol. 2020 May 04. pii: S0008-8749(20)30063-0. [Epub ahead of print]353 104119

The roles of tumor-associated macrophages in tumor angiogenesis and metastasis.

Luo-Qin Fu, Wen-Lin Du, Mao-Hua Cai, Jia-Yu Yao, Yuan-Yuan Zhao, Xiao-Zhou Mou.

Tumor associated macrophages (TAMs) are the most frequent immune cells within tumor microenvironment (TME). There is growing evidence that TAMs are involved in tumor progression via multiple mechanisms. TAMs create an immunosuppressive TME by producing growth factors, chemokines, and cytokines which modulate recruitment of immune cells and inhibit anti-tumor responses. They also serve as angiogenesis promoting cells by production of pro-angiogenic factors and matrix metalloproteinases (MMPs) and vascular constructing which guarantee supplying oxygen and nutrients to solid tumor cells. Furthermore, TAMs play important functions in tumor metastasis through contributing to invasion, extravasation, survival, intravasation, and colonization of tumor cells. In this review, we summarized macrophage classification, TAMs polarization, and mechanisms underlying TAM-promoting angiogenesis and metastasis.

Keywords: Angiogenesis; Metastasis; Tumor microenvironment; Tumor-associated macrophage

DOI: https://doi.org/10.1016/j.cellimm.2020.104119