Targeting tumor tolerance: A new hope for pancreatic cancer therapy?

Delitto, Daniel; Wallet, Shannon M.; Hughes, Steven J.

doi:10.1016/j.pharmthera.2016.06.008

Cited by 34 publications

(35 citation statements)

References 298 publications

(287 reference statements)

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“…Myeloidderived suppressor cells (MDSCs) are premature myeloid progenitor cells produced that suppress T cell function. The expansion of MDSCs is further promoted by tumourderived cytokines (Delitto et al 2016). Some inflamed tumours and many immune excluded tumours recruit MDSCs and secrete TGF-β, which creates a reactive immunosuppressive stroma that lacks an inflammatory milieu required for T cell infiltration and activation (Hegde et al 2016).…”

Section: :12mentioning

confidence: 99%

“…The development of algorithms to predict candidate neoantigens and immunogenicity of peptides with higher precision are the topic of intense current research efforts in academia and the private sector (Weber et al 2009, Zhang et al 2015. Such algorithms will be invaluable for the design of peptide vaccines and chimeric antigen receptor (CAR) T cell technology, where chimeras are generated by combining side-chain variable fragments with the ζ subunit of CD3, CD28 or CD137 to artificially link tumour surface antigen specificity with activation signal transmission in T cells upon antigen binding (Delitto et al 2016). Vaccines have had poor track record, as they largely focus on antigens not specific to tumours (non-neoantigens).…”

Section: Role Of Tumour Mutational Load In Cancer Immunitymentioning

confidence: 99%

“…Thus, the lower rate of somatic mutations may contribute to the poor immunogenicity of PCs and render these cancers resistant to checkpoint immunotherapy (Delitto et al 2016). Recent genomic profiling found that although the predicted number of neoantigens in pancreatic cancer samples is low, nearly all pancreatic ductal adenocarcinoma (PDAC) yielded potential targetable neoantigen candidates (Bailey et al 2016).…”

Section: Role Of Tumour Mutational Load In Cancer Immunitymentioning

confidence: 99%

“…Recent advances in immunotherapy have presented opportunities to eliminate cancers that were not achieved with previous standard of care therapies (Delitto et al 2016). Immune checkpoint inhibitor treatment has shown to be a tolerable therapy delivering very promising results in treating many cancer types including melanomas and lung cancer (Delitto et al 2016, Rafei et al 2017.…”

Section: Introductionmentioning

confidence: 99%

“…Immune checkpoint inhibitor treatment has shown to be a tolerable therapy delivering very promising results in treating many cancer types including melanomas and lung cancer (Delitto et al 2016, Rafei et al 2017. However, recurrence of cancers and variable success among different cancers are not uncommon.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The role of the tumour microenvironment in immunotherapy

Gasser

Lim

Cheung

2017

Endocrine-Related Cancer

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Recent success in immunomodulating strategies in lung cancer and melanoma has prompted much enthusiasm in their potential to treat other advanced solid malignancies. However, their applications have shown variable success and are even ineffective against some tumours. The efficiency of immunotherapies relies on an immunogenic tumour microenvironment. The current field of cancer immunology has focused on understanding the interaction of cancer and host immune cells to break the state of immune tolerance and explain how molecular patterns of cytokines and chemokines affect tumour progression. Here, we review our current knowledge of how inherent properties of tumours and their different tumour microenvironments affect therapeutic outcome. We also discuss insights into recent multimodal therapeutic approaches that target tumour immune evasion and suppression to restore anti-tumour immunity.

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Section: :12mentioning

confidence: 99%

Section: Role Of Tumour Mutational Load In Cancer Immunitymentioning

confidence: 99%

Section: Role Of Tumour Mutational Load In Cancer Immunitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of the tumour microenvironment in immunotherapy

Gasser

Lim

Cheung

2017

Endocrine-Related Cancer

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Overcoming the Tumor Microenvironmental Barriers of Pancreatic Ductal Adenocarcinomas for Achieving Better Treatment Outcomes

Alzhrani

Alsaab

Vanamal

et al. 2021

Advanced Therapeutics

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with the lowest survival rate among all solid tumors. The lethality of PDAC arises from late detection and propensity of the tumor to metastasize and develop resistance against chemo and radiation therapy. A highly complex tumor microenvironment composed of dense stroma, immune cells, fibroblast, and disorganized blood vessels, is the main obstacle to current PDAC therapy. Despite the tremendous success of immune checkpoint inhibitors (ICIs) in cancers, PDAC remains one of the poorest responders of ICIs therapy. The immunologically “cold” phenotype of PDAC is attributed to the low mutational burden, high infiltration of myeloid‐derived suppressor cells and T‐regs, contributing to a significant immunotherapy resistance mechanism. Thus, the development of innovative strategies for turning immunologically “cold” tumor into “hot” ones is an unmet need to improve the outcome of PDAC ICIs therapies. Other smart strategies, such as nanomedicines, sonic Hedgehog inhibitor, or smoothened inhibitor, are discussed to enhance chemotherapeutic agents' efficiency by disrupting the PDAC stroma. This review highlights the current challenges and various preclinical and clinical strategies to overcome current PDAC therapy difficulties, thus significantly advancing PDAC research knowledge.

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