干旱区生态环境知识资源中心(Arid): Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients

Arid

DOI	10.3390/cancers13061222
	Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients
	Frak, Malgorzata; Krawczyk, Pawel; Kalinka, Ewa; Milanowski, Janusz
通讯作者	Frak, M (corresponding author), Med Univ Lublin, Chair & Dept Pneumol Oncol & Allergol, PL-20954 Lublin, Poland.
来源期刊	CANCERS
EISSN	2072-6694
出版年	2021
卷号	13 期号:6
英文摘要	Simple Summary Immunotherapy is one of the most effective systemic treatment methods for many types of cancers. Unfortunately, cancer cells developed a number of defense mechanisms e.g., the absence of NK cells, macrophages or T lymphocytes in the tumor stroma, lack of pro-inflammatory cytokines in the tumor microenvironment (IL-6, IL-2, IL-12, TNF-alpha), production of immunosuppressive compounds (TGF-beta, indoleamine dioxygenase or neutralization of immune cells through direct immune checkpoints interactions (CD80/CD86 with CTLA-4 and PD-L1 with PD-1) that eventually make treatment ineffective. In this way, non-immunogenic, cold tumors are formed. The paper presents those mechanisms in details and focuses on the radiochemotherapy technique which, by neoantigen production, abscopal effect and activation of interferon synthesis pathways (STING), affects the production of cytokines and chemokines and transforms cold tumors into highly immunogenic hot, inflammatory tumors, susceptible to immunotherapy. Results are based on clinical trials conducted to date, which showed high effectiveness of the combination therapy consisting of radiochemotherapy and immunotherapy in NSCLC patients. Non-small cell lung cancer (NSCLC) is one of the most common malignancies around the world. Due to the advanced stage of the disease at the time of diagnosis, most patients require systemic treatment. Immunotherapy with immune checkpoints inhibitors is becoming the main treatment method for many cancers, including NSCLC. Numerous studies have shown greater efficacy of immunotherapy used monoclonal antibodies anti-PD-1 (pembrolizumab and nivolumab) or anti-PD-L1 (atezolizumab and durvalumab) compared to chemotherapy. Unfortunately, cancer cells can develop a number of mechanisms to escape from immune surveillance, including avoidance of cancer cells by the immune system (immune desert), production of immunosuppressive compounds (prostaglandins, IDO, TGF-beta), or direct immune checkpoints interactions. Therapy based on the use of radiochemotherapy with subsequent immunotherapy is becoming the main focus of research in the field of new NSCLC therapies. Radiation therapy stimulates the immune response multidirectionally, affects production of neoantigens and proinflammatory compounds, which transform non-immunogenic (cold) tumors into highly immunogenic (hot) tumors. As a result, the mechanisms of escape of cancer cells from immune surveillance break down and the effectiveness of immunotherapy increases significantly. The results of clinical trials in this area bring new hope and indicate greater effectiveness of such treatment in terms of prolongation of progression-free survival and overall survival.
英文关键词	non-small cell lung cancer radiotherapy immunotherapy PD-1 PD-L1
类型	Review
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000634349800001
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/349780
作者单位	[Frak, Malgorzata; Krawczyk, Pawel; Milanowski, Janusz] Med Univ Lublin, Chair & Dept Pneumol Oncol & Allergol, PL-20954 Lublin, Poland; [Kalinka, Ewa] Polish Mothers Mem Hosp, Res Inst Lodz, Dept Oncol, PL-93338 Lodz, Poland
推荐引用方式 GB/T 7714	Frak, Malgorzata,Krawczyk, Pawel,Kalinka, Ewa,et al. Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients[J],2021,13(6).
APA	Frak, Malgorzata,Krawczyk, Pawel,Kalinka, Ewa,&Milanowski, Janusz.(2021).Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients.CANCERS,13(6).
MLA	Frak, Malgorzata,et al."Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients".CANCERS 13.6(2021).