Plasmacytoid Dendritic Cells and Cancer Immunotherapy

Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement of DC-based vaccines as mono-immunotherapy or combinational immunotherapies. One exciting development is recent clinical studies with naturally circulating DCs including plasmacytoid DCs (pDCs). pDC vaccines were particularly intriguing, as pDCs are generally presumed to play a negative role in regulating T cell responses in tumors. Similarly, DC-derived exosomes (DCexos) have been heralded as cell-free therapeutic cancer vaccines that are potentially superior to DC vaccines in overcoming tumor-mediated immunosuppression, although DCexo clinical trials have not led to expected clinical outcomes. Using a pDC-targeted vaccine model, we have recently reported that pDCs required type 1 conventional DCs (cDC1s) for optimal cross-priming by transferring antigens through pDC-derived exosomes (pDCexos), which also cross-prime CD8 T cells in a bystander cDC-dependent manner. Thus, pDCexos could combine the advantages of both cDC1s and pDCs as cancer vaccines to achieve better anti-tumor efficacy. In this review, we will focus on the pDC-based cancer vaccines and discuss potential clinical application of pDCexos in cancer immunotherapy.

Vaccination against Cancer or Infectious Agents during Checkpoint Inhibitor Therapy

The use of immune checkpoint inhibitors (ICI) has substantially increased the overall survival of cancer patients and has revolutionized the therapeutic situation in oncology. However, not all patients and cancer types respond to ICI, or become resistant over time. Combining ICIs with therapeutic cancer vaccines is a promising option as vaccination may help to overcome resistance to immunotherapies while immunotherapies may increase immune responses to the particular cancer vaccine by reinvigorating exhausted T cells. Thus, it would be possible to reprogram a response with appropriate vaccines, using a particular cancer antigen and a corresponding ICI. Target populations include currently untreatable cancer patients or those who receive treatment regimens with high risk of serious side effects. In addition, with the increased use of ICI in clinical practice, questions arise regarding safety and efficacy of administration of conventional vaccines, such as influenza or COVID-19 vaccines, during active ICI treatment. This review discusses the main principles of prophylactic and therapeutic cancer vaccines, the potential impact on combining therapeutic cancer vaccines with ICI, and briefly summarizes the current knowledge of safety and effectiveness of influenza and COVID-19 vaccines in ICI-treated patients.

Vaccines as Priming Tools for T Cell Therapy for Epithelial Cancers

Impressive progress has recently been made in the field of cancer immunotherapy with the adoptive transfer of T cells, a successful personalized strategy, and checkpoint inhibitors (CPI) having extended the survival of numerous patients. However, not all patients have been able to benefit from these innovations. A key determinant of the responsiveness to cancer immunotherapies is the presence of T cells within the tumors. These tumor-infiltrating lymphocytes (TILs) are crucial in controlling tumor growth and their activity is being potentiated by immunotherapies. Although some epithelial cancers are associated with spontaneous T-cell and B-cell responses, which makes them good candidates for immunotherapies, it remains to create strategies that would promote lymphocyte infiltration and enable sustained immune responses in immune-resistant tumors. Therapeutic cancer vaccines hold the potential of being able to render “cold”, poorly infiltrated tumors into “hot” tumors that would be receptive to cellular immunotherapies. In this review, we elaborate on the obstacles that need to be overcome and the strategies that are being explored to that end, including various types of antigen repertoires and different vaccine platforms and combinations with other available treatments.

Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment

In this editorial, we highlight articles published in this Special Issue of Vaccines on “Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment”, recent developments in the field of cancer vaccines, and the potential for immunotherapeutic combinations in cancer care. This issue covers important developments and progress being made in the cancer vaccine field and possible future directions for exploring new technologies to produce optimal immune responses against cancer and expand the arena of prophylactic and therapeutic cancer vaccines for the treatment of this deadly disease.

Clinical Application of Adaptive Immune Therapy in MSS Colorectal Cancer Patients

Colorectal cancer (CRC) is one of the most common cancers worldwide. However, the treatment outcomes of immunotherapy in microsatellite-stable (MSS) CRC remain unsatisfactory. As the majority of CRC cases display a molecular MSS/mismatch repair-proficient (pMMR) profile, it is particularly meaningful to explore the clinical applications of adaptive immune therapy in MSS CRC patients. In this review, we summarized the therapeutic approaches of adoptive immune therapies, including cytokines, therapeutic cancer vaccines, adoptive T-cell therapy, and immune checkpoint inhibitors, in the treatment of MSS CRCs.

Vaccines for Non-Viral Cancer Prevention

Cancer vaccines are a type of immune therapy that seeks to modulate the host’s immune system to induce durable and protective immune responses against cancer-related antigens. The little clinical success of therapeutic cancer vaccines is generally attributed to the immunosuppressive tumor microenvironment at late-stage diseases. The administration of cancer-preventive vaccination at early stages, such as pre-malignant lesions or even in healthy individuals at high cancer risk could increase clinical efficacy by potentiating immune surveillance and pre-existing specific immune responses, thus eliminating de novo appearing lesions or maintaining equilibrium. Indeed, research focus has begun to shift to these approaches and some of them are yielding encouraging outcomes.

Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advanced HCC, including immune checkpoint inhibitors, adoptive cell therapy, engineered cytokines, and therapeutic cancer vaccines. In this review, we summarize the current landscape and research progress of different immunotherapy strategies in the treatment of HCC. The challenges and opportunities of this research field are also discussed.

Therapeutic cancer vaccines: reasons to believe

Our hopes of using the power of the immune system to control tumours have been partially fulfilled with anti-PD1 antibodies and other checkpoint inhibitors and the use of engineered T cells targeting lineage-specific surface markers with chimeric antigen receptors. Can these successes be generalised? Therapeutic cancer vaccines aim to educate or re-educate the immune system to recognise tumour specific or tumour associated antigens. After many false dawns, some positive data for the effectiveness of such an approach is starting to emerge in advanced solid tumours, albeit as combination therapies with checkpoint inhibitors. But is the field targeting the right antigens? Interventions using the most effective vaccine platforms to target certain sets of antigens in patients with low disease burden might bring impressive long-term benefits to patients as single agents.