Knockdown of end-binding protein 1 induces apoptosis in radioresistant A549 lung cancer cells via p38 kinase-dependent COX-2 upregulation

Mortezaee

2018

1,177

853

CD8+ cytotoxic T lymphocytes (CTLs) are preferred immune cells for targeting cancer. During cancer progression, CTLs encounter dysfunction and exhaustion due to immunerelated tolerance and immunosuppression within the tumor microenvironment (TME), with all favor adaptive immune‐resistance. Cancer‐associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and regulatory T cells (Tregs) could make immunologic barriers against CD8 + T cell‐mediated antitumor immune responses. Thus, CD8 + T cells are needed to be primed and activated toward effector CTLs in a process called tumor immunity cycle for making durable and efficient antitumor immune responses. The CD8 + T cell priming is directed essentially as a corroboration work between cells of innate immunity including dendritic cells (DCs) and natural killer (NK) cells with CD4 + T cells in adoptive immunity. Upon activation, effector CTLs infiltrate to the core or invading site of the tumor (so‐called infiltrated–inflamed [I–I] TME) and take essential roles for killing cancer cells. Exogenous reactivation and/or priming of CD8 + T cells can be possible using rational immunotherapy strategies. The increase of the ratio for costimulatory to coinhibitory mediators using immune checkpoint blockade (ICB) approach. Programmed death‐1 receptor (PD‐1)–ligand (PD‐L1) and CTL‐associated antigen 4 (CTLA‐4) are checkpoint receptors that can be targeted for relieving exhaustion of CD8 + T cells and renewing their priming, respectively, and thereby eliminating antigen‐expressing cancer cells. Due to a diverse relation between CTLs with Tregs, the Treg activity could be dampened for increasing the number and rescuing the functional potential of CTLs to induce immunosensitivity of cancer cells.

Section: Nk Cellsmentioning

confidence: 99%

CD8⁺ cytotoxic T lymphocytes in cancer immunotherapy: A review

Farhood

Mortezaee

2018

1,177

853

“…Activation of the P38/COX‐2 signaling (J.‐H. Baek et al, ) induces ROS overproduction (Z. Xu et al, ) that is further contributed to promotion of apoptosis in cancers like osteosarcoma. For glioma, there are two opposite views for the roles of COX‐2 overexpression with either enhancement of cancer promotion through interaction between COX‐2 with NF‐κβ (X. Wang, Yu, et al, ; J. Zhao, Zhu, et al, ), WNT (Wu et al, ), and EGFR (J. Li, Zhou, et al, ) for respective induction of inflammation, CSC activity and survival in cancer cells, or suppression of tumor progression through possible interaction between COX‐2 with the endocannabinoid system that further elicits proapoptotic actions in this system (Hinz, Ramer, Eichele, Weinzierl, & Brune, ).…”

Section: Cox‐2 As An Anticancer Enzymementioning

confidence: 99%

Cyclooxygenase‐2 in cancer: A review

Goradel

Salehi

et al. 2018

562

399

Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo-and radiotherapy. COX-2 is released by cancerassociated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX-2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX-2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX-2 on cancer cells or its regulation. Members of mitogen-activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor-κβ are main upstream modulators for COX-2 in cancer cells. COX-2 also has interactions with a number of hormones within the body. Inhibition of COX-2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX-2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX-2 inhibition also sensitizes cancer cells to treatments like radioand chemotherapy. Chemotherapeutic agents adversely induce COX-2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX-2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer.

“…NK cells are essential components of innate immunity for combatting tumor progression. The cells are capable of recognizing and killing cancer cells without a requirement for antigen exposure (Baek et al, 2018). NK cells have antitumor ability in an immature state, while differentiated NK cells acquire PD-1 receptor that is expressed at a considerable rate upon tumor progression (Albini, Bruno, Noonan, & Mortara, 2018).…”

Section: Nk Cellsmentioning

confidence: 99%

Contribution of regulatory T cells to cancer: A review

Farhood

Mortezaee

2018

154

103

Regulatory T cells (Tregs) represent a low number of T‐cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross‐talks with other immunosuppressive cells including cancer‐associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid‐derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor‐β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor‐bearing receptors in Tregs, including FOXP3, programmed death‐1, T‐cell immunoglobulin mucin‐3, and CTL‐associated antigen‐4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.