Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family–interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p–mediated repression on apoptotic gene Bak1. Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity. Tumor-derived lactate translationally inhibits FIP200 expression by down-regulating the nicotinamide adenine dinucleotide level while potentially up-regulating the inhibitory effect of adenylate-uridylate–rich elements within the 3′ untranslated region of Fip200 mRNA. Thus, tumors metabolically target naïve T cells to evade immunity.

Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in the development of many cancers by affecting tumor growth or metastasis. Thanks to recent advances in single-cell technologies, the nature of monocyte heterogeneity and subset-specific functions have become increasingly clear, making it possible to systematically analyze subset-specific roles of monocytes in tumorigenesis. In this review, we discuss recent discoveries related to monocytes and tumorigenesis, and new strategies for tumor biomarker identification and anti-tumor immunotherapy.

Macrophages residing in various tissues play crucial roles in innate immunity, tissue repair, and immune homeostasis. The development and differentiation of macrophages in non-lymphoid tissues are highly regulated by the tissue microenvironment. Peritoneum provides a unique metastatic niche for certain types of tumor cells. As the dominant immune cell type in peritoneal cavity, macrophages control the immune response to tumor and influence the efficacy of anti-tumor therapy. Considering the heterogeneity of macrophages in origin, metabolism, and function, it is always challenging to define the precise roles of macrophages in tumor microenvironment. We review here recent progresses in peritoneal resident macrophage research in the context of physiological and metastatic tumor conditions, which may benefit the development of new anti-tumor therapies through targeting macrophages.

Macrophages, as the predominant phagocytes, play an essential role in pathogens defense and tissue homeostasis maintenance. In the context of cancer, tumor-associated macrophages (TAMs) have evolved into cunning actors involved in angiogenesis, cancer cell proliferation and metastasis, as well as the construction of immunosuppressive microenvironment. Once properly activated, macrophages can kill tumor cells directly through phagocytosis or attack tumor cells indirectly by stimulating innate and adaptive immunity. Thus, the prospect of targeting TAMs has sparked significant interest and emerged as a promising strategy in immunotherapy. In this review, we summarize the diverse roles and underlying mechanisms of TAMs in cancer development and immunity and highlight the TAM-based therapeutic strategies such as inhibiting macrophage recruitment, inhibiting the differentiation reprogramming of TAMs, blocking phagocytotic checkpoints, inducing trained macrophages, as well as the potential of engineered CAR-armed macrophages in cancer therapy.

It is currently widely accepted that immune activation in HIV-infected individuals leads to a severe loss of CD4⁺ T cells and the progression to AIDS. However, the underlying mechanism of this immune activation remains unclear. Experimental data suggest that the activation of plasmacytoid dendritic cells (pDCs) by plasma viremia may play a critical role in HIV-induced immune activation. In this study, we found that the level of immune activation was higher in the late phase of SIVmac239 infection compared with chronic infection, which suggests that immune activation might be related to disease progression in SIVmac239-infected non-human primate models. Our work also showed that chloroquine could effectively inhibit the activation of pDCs in vitro and in vivo. However, chloroquine treatment of SIVmac239-infected macaques had no significant influence on the Cellular composition of peripheral blood in these animals.