Maccalli Cristina, Parmiani Giorgio, Ferrone Soldano
a Department of Translational Medicine , Sidra Medical and Research Center , Doha , Qatar.
b Italian Network for Biotherapy, University Hospital of Siena , Siena , Italy.
Immunol Invest. 2017 Apr;46(3):221-238. doi: 10.1080/08820139.2017.1280051. Epub 2017 Mar 13.
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy.
ALDH, aldehyde dehydrogenase; APC, antigen-presenting cells; APM, antigen-processing machinery; CAR: chimeric antigen receptor; CHK1, checkpoint serine/threonine protein kinase; CIC, cancer-initiating cell; CRC, colorectal cancer; CTLA-4, cytotoxic T lymphocyte antigen-4; GBM, glioblastoma multiforme; GDF-15, growth differentiation factor-15; CSPG4: chondroitin sulfate proteoglycan-4; IFN, interferon; IL-4, interleukin-4; IL-10, interleukin-10; IL-13, interleukin-13; IL-13α2, α2 chain of IL-13 receptor; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1 programmed death ligand-1; PDK, 3-phosphoinositide-dependent protein kinase-1; PGE2, prostaglandin E2; STAT3, signal transducer and activator of transcription 3; TGFB-1, transforming growth factor beta-1; Treg, T regulatory cell.
癌症起始细胞（CICs）是一类相对罕见的细胞亚群，具有自我更新、干性特征、在免疫缺陷小鼠中具有致瘤性，并且对标准疗法以及免疫疗法具有抗性。在此，我们综述了CICs的生物学和免疫学特征，特别关注它们用于逃避免疫监视的免疫调节机制。最近开发的免疫治疗策略在许多类型的肿瘤中取得了显著的临床效果，这表明患者的免疫系统确实可以产生有效的免疫反应来控制肿瘤生长。然而，很大一部分患者对这些治疗策略具有抗性或获得抗性。后一发现至少在某些情况下可能反映了所使用的免疫治疗策略无法根除CICs。逃避免疫识别和破坏的CICs可能在同一器官部位产生新肿瘤，或通过转移定植在其他解剖部位产生新肿瘤。识别能够根除CICs的新型治疗方法是癌症治疗领域的一项重大挑战。更好地理解CICs与免疫系统以及肿瘤微环境之间的相互作用，可能有助于优化现有疗法并设计新型癌症治疗联合方案。
ALDH，醛脱氢酶；APC，抗原呈递细胞；APM，抗原加工机制；CAR：嵌合抗原受体；CHK1，检查点丝氨酸/苏氨酸蛋白激酶；CIC，癌症起始细胞；CRC，结直肠癌；CTLA-4，细胞毒性T淋巴细胞抗原-4；GBM，多形性胶质母细胞瘤；GDF-15，生长分化因子-15；CSPG4：硫酸软骨素蛋白聚糖-4；IFN，干扰素；IL-4，白细胞介素-4；IL-10，白细胞介素-10；IL-13，白细胞介素-13；IL-13α2，IL-13受体α2链；mAb，单克隆抗体；MDSC，髓源性抑制细胞；MHC，主要组织相容性复合体；PD-1，程序性死亡-1；PD-L1程序性死亡配体-1；PDK，3-磷酸肌醇依赖性蛋白激酶-1；PGE2，前列腺素E2；STAT3，信号转导和转录激活因子3；TGFB-1，转化生长因子β-1；Treg，调节性T细胞。
