Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
Adv Protein Chem Struct Biol. 2024;140:249-292. doi: 10.1016/bs.apcsb.2024.02.004. Epub 2024 Apr 6.
Cancer is no longer recognized as a single disease but a collection of diseases each with its defining characteristics and behavior. Even within the same cancer type, there can be substantial heterogeneity at the molecular level. Cancer cells often accumulate various genetic mutations and epigenetic alterations over time, leading to a coexistence of distinct subpopulations of cells within the tumor. This tumor heterogeneity arises not only due to clonal outgrowth of cells with genetic mutations, but also due to interactions of tumor cells with the tumor microenvironment (TME). The latter is a dynamic ecosystem that includes cancer cells, immune cells, fibroblasts, endothelial cells, stromal cells, blood vessels, and extracellular matrix components, tumor-associated macrophages and secreted molecules. The complex interplay between tumor heterogeneity and the TME makes it difficult to develop one-size-fits-all treatments and is often the cause of therapeutic failure and resistance in solid cancers. Technological advances in the post-genomic era have given us cues regarding spatial and temporal tumor heterogeneity. Armed with this knowledge, oncologists are trying to target the unique genomic, epigenetic, and molecular landscape in the tumor cell that causes its oncogenic transformation in a particular patient. This has ushered in the era of personalized precision medicine (PPM). Immunotherapy, on the other hand, involves leveraging the body's immune system to recognize and attack cancer cells and spare healthy cells from the damage induced by radiation and chemotherapy. Combining PPM and immunotherapy represents a paradigm shift in cancer treatment and has emerged as a promising treatment modality for several solid cancers. In this chapter, we summarise major types of cancer immunotherapy and discuss how they are being used for precision medicine in different solid tumors.
癌症不再被认为是一种单一的疾病,而是一组具有各自定义特征和行为的疾病。即使在同一癌症类型中,分子水平上也可能存在很大的异质性。癌细胞随着时间的推移经常积累各种遗传突变和表观遗传改变,导致肿瘤内不同细胞亚群的共存。这种肿瘤异质性的产生不仅是由于具有遗传突变的细胞的克隆性生长,还与肿瘤细胞与肿瘤微环境(TME)的相互作用有关。后者是一个动态的生态系统,包括癌细胞、免疫细胞、成纤维细胞、内皮细胞、基质细胞、血管和细胞外基质成分、肿瘤相关巨噬细胞和分泌分子。肿瘤异质性和 TME 之间的复杂相互作用使得开发一刀切的治疗方法变得困难,这通常是实体癌治疗失败和耐药的原因。后基因组时代的技术进步为我们提供了关于时空肿瘤异质性的线索。肿瘤学家利用这些知识,试图针对导致特定患者肿瘤发生致癌转化的肿瘤细胞的独特基因组、表观遗传和分子景观进行靶向治疗。这开创了个性化精准医学(PPM)的时代。另一方面,免疫疗法涉及利用人体免疫系统识别和攻击癌细胞,使健康细胞免受放疗和化疗引起的损伤。将 PPM 和免疫疗法相结合代表了癌症治疗的范式转变,并已成为几种实体癌的一种有前途的治疗方式。在本章中,我们总结了主要类型的癌症免疫疗法,并讨论了它们如何在不同的实体肿瘤中用于精准医学。