The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8⁺ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses.

Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another. However, during this co-evolution the discovery of a subset of long-lived NK cells with enhanced effector potential, increased antibody-dependent responses and the potential to mediate immune memory has revolutionized the field of NK cell biology. The ability of a virus to imprint on the NK cell receptor repertoire resulting in the expansion of diverse, highly functional NK cells to this day remains a significant immunological phenomenon that only occurs in the context of CMV. Here we review our current understanding of the development of these NK cells, commonly referred to as adaptive NK cells and their current role in transplantation, infection, vaccination and cancer immunotherapy to decipher the complex role of CMV in dictating NK cell functional fate.

Despite advances in immunotherapy, metastatic melanoma remains a considerable therapeutic challenge due to the complexity of the tumor microenvironment. Intratumoral type I interferon (IFN-I) has long been associated with improved clinical outcomes. However, several IFN-I subtypes can also paradoxically promote tumor growth in some contexts. We investigated this further by engineering murine B16 melanoma cells to overexpress various IFN-I subtypes, where a spectrum of outcomes was observed. Characterization of these tumors by RNA sequencing revealed a tumor immune phenotype, where potent IFN-I signaling concomitant with diminished type 2 inflammation failed to confer durable tumor control. T cell–mediated rejection of these tumors was restored by introducing interleukin-4 (IL-4) into the tumor microenvironment, either through ectopic expression or in a preclinical adoptive T cell therapy model. Collectively, our findings highlight the IFN-I/IL-4 axis in promoting antitumor immunity, which could be harnessed to target and stratify solid tumors that are nonresponsive to frontline therapies.

Recent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself. Burn injury has also been shown to induce sustained immune system dysfunction. This change to immune function may contribute to the increased risk of chronic disease observed. However, the mechanisms that disrupt long-term immune function in response to burn trauma, and their link to long-term morbidity, remain unknown. In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury. An established mouse model of non-severe burn injury (full thickness burn equivalent to 8% total body surface area) was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer. Considering that CD8⁺ T cells are important drivers of effective tumour suppression in this model, we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection. Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function. We demonstrate that 4 weeks after a non-severe burn injury, mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma. In addition, our results reveal that CD8⁺ T cell expansion, differentiation and memory potential is significantly impaired at 1 month post-burn. Our data suggests that CD8⁺ T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury. Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.

Immunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far. A significant focus to date has been the identification of specific markers associated with response to immunotherapy. Unfortunately, the heterogeneity between patients and cancer types means identifying markers of response to therapy is inherently complex. There is a growing appreciation for the role of the tumour microenvironment (TME) in directing response to immunotherapy. The TME is highly heterogeneous and contains immune, stromal, vascular and tumour cells that all communicate and interact with one another to form solid tumours. This review analyses major cell populations present within the TME with a focus on their diverse and often contradictory roles in cancer and how this informs our understanding of immunotherapy. Furthermore, we discuss the role of integrated omics in providing a comprehensive view of the TME and demonstrate the potential of leveraging multi-omics to decipher the underlying mechanisms of anti-tumour immunity for the development of novel immunotherapeutic strategies.