Cell-based cancer immunotherapy, such as chimeric antigen receptor (CAR) engineered T and natural killer (NK) cell therapies, has become a revolutionary new pillar in cancer treatment. Interleukin 15 (IL-15), a potent immunostimulatory cytokine that potentiates T and NK cell immune responses, has demonstrated the reliability and potency to potentially improve the therapeutic efficacy of current cell therapy. Structurally similar to interleukin 2 (IL-2), IL-15 supports the persistence of CD8⁺ memory T cells while inhibiting IL-2-induced T cell death that better maintains long-term anti-tumor immunity. In this review, we describe the biology of IL-15, studies on administrating IL-15 and/or its derivatives as immunotherapeutic agents, and IL-15-armored immune cells in adoptive cell therapy. We also discuss the advantages and challenges of incorporating IL-15 in cell-based immunotherapy and provide directions for future investigation.

The discovery of receptor clustering in the activation of adaptive immune cells has revolutionized our understanding of the physical basis of immune signal transduction. In contrast to the extensive studies of adaptive immune cells, particularly T cells, there is a lesser, but emerging, recognition that the formation of receptor clusters is also a key regulatory mechanism in host–pathogen interactions. Many kinds of innate immune receptors have been found to assemble into nano- or micro-sized domains on the surfaces of cells. The clusters formed between diverse categories of innate immune receptors function as a multi-component apparatus for pathogen detection and immune response regulation. Here, we highlight these pioneering efforts and the outstanding questions that remain to be answered regarding this largely under-explored research topic. We provide a critical analysis of the current literature on the clustering of innate immune receptors. Our emphasis is on studies that draw connections between the phenomenon of receptor clustering and its functional role in innate immune regulation.

Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an “unlimited supply” for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (γδ T), mucosal-associated invariant T (MAIT) cells, and macrophages (Mφs). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT and iPSC-Mφ), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.

The clustering of TLR1/2 acts as a driver in integrating the spatial cues of ligands into cell-level activation events.

The term cellular immune response refers to haemocyte-mediated responses, including phagocytosis, nodulation, and encapsulation. In the present study, we identified five types of circulating haemocytes in larvae of the haemolymph of the Asian corn borer, Ostrinia furnacalis (Guen?e), including granulocytes, oenocytoids, plasmatocytes, prohaemocytes, and spherulocytes. The relative number of total free haemocytes per larva decreased significantly 0.5, 24, and 36 h after the injection of Beauveria bassiana conidia. Upon conidia challenge, both phagocytosis and nodulation were observed in the collected haemolymph from O. furnacalis larvae. In addition, plasma was found to be necessary for both phagocytosis and nodulation. Therefore, we here confirm that phagocytosis and nodulation are involved in O. funacalis larvae during their fight against infection by B. bassiana, and further, that the cellular immune response of O. furnacalis helps eliminate the invading organisms despite the fact that not all the fungal conidia are killed.