Current Status of Immunotherapies for Treating Pancreatic Cancer

Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

“…This consistent pattern in VISTA contrasts that for other immune checkpoint molecules that were not appreciably altered. Considering the downregulation of biomarkers related to T cells and immune checkpoints, it emphasizes the need for identifying other therapeutic modalities (i.e., vaccines, TLR agonists) that might act to increase the number and quality of infiltrating T cells into PDAC tumors (23)(24)(25).…”

Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy

“…Surprisingly, the potential in combining the immunomodulatory effects of Src-inhibitors with other immunomodulatory therapies has not been extensively studied. This could be particularly relevant in pancreatic cancer where immunotherapy provides no therapeutic benefit as a result of the immunosuppressive microenvironment that defines these tumours [166]. However in a clinical study of gastrointestinal stromal tumours (GIST), dasatinib and anti-CTLA4 antibody ipilimumab were well tolerated yet the combination was not synergistic, potentially due to the lack of a biomarker-driven approach [165].…”

“…However due to the strong immunomodulatory effects of Src inhibition seen in vivo, assessment of synergistic combinatorial therapies including dasatinib and other immunomodulatory drugs is warranted. This could be particularly relevant in pancreatic cancer where immunotherapy provides no therapeutic benefit as a result of the immunosuppressive microenvironment that defines these tumours [166]. Combining Src inhibition with additional targeted therapies is another potentially beneficial approach aimed at enhancing antitumour efficacy, while minimising inherent and acquired resistance.…”

Selective tumor antigen vaccine delivery to human CD169 + antigen-presenting cells using ganglioside-liposomes

“…Patients with pancreatic cancer, for example, failed to respond to monotherapies of checkpoint inhibitors in multiple trials (2,3). Factors such as poor tumor immunogenicity, tumorimmunosuppressive microenvironment, and the lack of an existing tumor-specific immune response are thought to contribute to patients' lack of response to these immune-checkpoint inhibitors (2,4,5). Nevertheless, the abundance of intratumoral CD8 + T cells is associated with longer survival of pancreatic cancer patients, suggesting these patients may benefit from a better antitumor immunity (6)(7)(8).…”