Bolon Brad, Aeffner Famke
1 GEMpath, Inc., Longmont, Colorado, USA.
2 Flagship Biosciences, Westminster, Colorado, USA.
Toxicol Pathol. 2017 Jul;45(5):584-588. doi: 10.1177/0192623317713318. Epub 2017 Jun 21.
Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis. Therapeutic modalities to address these targets include administering antibodies, cytokines, or small molecules that directly stimulate the immune system, attack tumor-associated antigens, or interfere with tumor-stroma interactions; adoptive transfer of autologous T cells following ex vivo selection/expansion/activation (typically after lymphoid-depleting regimens and in conjunction with immunostimulatory therapy); and vaccination (against tumor antigens). Pathology involvement in oncoimmunology product development is critical to assess expression of target molecules in tumor cells, stromal cells, and tumor-infiltrating leukocytes.
肿瘤免疫学(或免疫肿瘤学)是精准(“个性化”)医学中一个新兴的专业领域,旨在增强免疫系统针对肿瘤细胞过度表达或仅由肿瘤细胞表达的分子的抗肿瘤反应。这种关注是必要的,因为癌症是由抗原性异质性细胞组成的多克隆组织,其确切组成由抗肿瘤免疫和促肿瘤炎症之间的平衡所塑造。关键靶点包括增强免疫系统(尤其是T细胞)反应性、抑制免疫检查点以及促进肿瘤细胞溶解。针对这些靶点的治疗方式包括施用直接刺激免疫系统、攻击肿瘤相关抗原或干扰肿瘤-基质相互作用的抗体、细胞因子或小分子;在体外选择/扩增/激活后(通常在淋巴细胞清除方案后并结合免疫刺激疗法)进行自体T细胞的过继性转移;以及接种疫苗(针对肿瘤抗原)。病理学参与肿瘤免疫产品开发对于评估肿瘤细胞、基质细胞和肿瘤浸润白细胞中靶分子的表达至关重要。