Immune contexture defined by single cell technology for prognosis prediction and immunotherapy guidance in cancer

Tumor immune microenvironment is closely related to tumor initiation,prognosis,and response to immunotherapy.The immune landscapes,number of infiltrating immune cells,and the localization of lymphocytes in the tumor vary in across different types of tumors.The immune contexture in cancer,which is determined by the density,composition,functional state and organization of the leukocyte infiltrate of the tumor,can yield information relevant to the prediction of treatment response and patients’prognosis.Better understanding of the immune atlas in human tumors have been achieved with the development and application of single-cell analysis technology,which has provided a reference for prognosis,and insights on new targets for immunotherapy.In this review,we summarized the different characteristics of immune contexture in cancer defined by a variety of single-cell techniques,which have enhanced our understanding on the pathophysiology of the tumor microenvironment.We believe that there are much more to be uncovered in this rapidly developing field of medicine,and they will predict the prognosis of cancer patients and guide the rational design of immunotherapies for success in cancer eradication.

Unlocking T cell exhaustion:Insights and implications for CAR-T cell therapy

Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen(BCMA)for hematological malignancies,albeit with moderate outcomes in solid tumors.However,despite these advancements,the efficacy of CAR-T therapy is often compromised by T cell exhaustion,a phenomenon that impedes the persistence and effector function of CAR-T cells,leading to a relapse rate of up to 75%in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies.Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies.In this review,we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy.These insights,combined with lessons learned from benchmarking CAR-T based products in recent clinical trials,aim to address the challenges posed by T cell exhaustion,potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.