Immunotherapy for pancreatic cancer: A long and hopeful journey

Xu, Jianwei; Wang, Lei; Cheng, Yugang; Zhang, Guangyong; Hu, Sanyuan; Zhou, Bin; Zhan, Hanxiang

doi:10.1016/j.canlet.2018.03.040

Cited by 41 publications

(33 citation statements)

References 94 publications

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“…Its aggressiveness partially depends on the extent of cancer-associated inflammation in its abundant stroma, which accounts for >90% of the tumor mass [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. A marked infiltration of immunosuppressive inflammatory cells into the tumor stroma is considered an early and consistent event in oncogenesis and tumor progression [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. From the early stages of tumor initiation, immunosuppressive regulatory T lymphocytes and Gr1 + CD11b + myeloid-derived suppressor cells are recruited to the tumor stroma, restraining the T-cell-mediated antitumor immunity [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is characterized by an abundant stromal component that comprises up to 90% of its total volume [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. The tumor stroma contains a highly immunosuppressive microenvironment resulting from the crosstalk between tumor and immune cells, which promotes oncogenesis and tumor progression [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Emerging immunotherapies, including anti-PD-1 (PDCD1)/PD-L1 (CD274) antibodies, have been used effectively to treat several types of cancers, including non-small-cell lung cancer (NSCLC) and malignant melanoma [ 11 , 12 ]; however, these therapies lack efficacy in treating pancreatic cancers, partly due to their abundant stroma with an immunosuppressive microenvironment [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…The tumor stroma contains a highly immunosuppressive microenvironment resulting from the crosstalk between tumor and immune cells, which promotes oncogenesis and tumor progression [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Emerging immunotherapies, including anti-PD-1 (PDCD1)/PD-L1 (CD274) antibodies, have been used effectively to treat several types of cancers, including non-small-cell lung cancer (NSCLC) and malignant melanoma [ 11 , 12 ]; however, these therapies lack efficacy in treating pancreatic cancers, partly due to their abundant stroma with an immunosuppressive microenvironment [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 13 , 14 , 15 , 16 , 17 , 18 ]. To improve the outcomes in patients with pancreatic cancer, it is critical to identify the mechanisms underlying the tumor microenvironment as well as new molecular targets for the development of effective strategies against this fatal cancer type [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Inamura

Takazawa

Inoue

et al. 2018

JCM

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B7-H3 (CD276), a member of the family of immune modulators, orchestrates antitumor immunity. To date, only small-sized studies have examined the association of B7-H3 expression with survival in pancreatic cancer, yielding inconclusive results. We evaluated tumor B7-H3 expression in 150 consecutive patients with pancreatic ductal adenocarcinoma using immunohistochemistry. B7-H3 expression was positive (≥10% tumor cells) in 99 of 150 (66%) cases of pancreatic cancer. We classified the tumors into four groups depending on B7-H3 expression (negative, low, intermediate, and high) and found that higher B7-H3 expression was independently associated with lower disease-free survival (DFS; for high vs. negative B7-H3 expression: multivariable hazard ratio (HR) = 3.12; 95% confidence interval (CI) = 1.48–6.15; Ptrend = 0.0026). Furthermore, the association of B7-H3 expression with survival differed according to the pathological stage (p-stage) (Pinteraction = 0.048, between p-stages I–II and III–IV). The association of B7-H3 positivity with lower DFS was stronger in tumors with p-stage I–II (multivariable HR = 3.10, 95% CI = 1.75–5.69; P < 0.0001) than in those with p-stage III–IV (multivariable HR = 1.20, 95% CI = 0.67–2.28; P = 0.55). We demonstrated that tumor high B7-H3 expression is independently associated with poor survival in patients with pancreatic cancer and that this association is stronger in tumors with p-stage I–II than in those with p-stage III–IV. B7-H3 expression may be a useful prognostic biomarker for identifying aggressive early-stage pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Inamura

Takazawa

Inoue

et al. 2018

JCM

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“…This distribution may be due to the higher efficacy of CAR-T and PD1 on hematologic tumors and melanoma, respectively [ 19 – 22 ]. There were few counts for several tumors with poor prognosis such as pancreatic cancer and gastric cancer, and this may due to their limited response to immunotherapy [ 23 ]. With in-depth study of the mechanism of tumor immunotherapy, there is opportunity for study of malignant tumors with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Bibliometric Analysis of Tumor Immunotherapy Studies

et al. 2018

Med Sci Monit

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BackgroundCancer immunotherapy is the use of the immune system to treat cancer. After years of research, there have been a significant number of publications in this field. We analyzed the literature and performed a hotspot analysis to identify important areas of future scientific research.Material/MethodsArticles (2945) related to cancer immunotherapy published in the past 3 years were selected as the research sample. BICOMB software was then used to retrieve the high-frequency words and construct a text/co-word matrix. Next, gCLUTO software was used to analyze the matrix by double-clustering and visual analysis, in a strategy of hotspot identification.ResultsWe constructed a text and co-word matrix composed of 40 high-frequency words and 2945 articles and generated a hotspot “peak map” based on double-clustering analysis. The strategic coordinates were set by use of a co-word matrix and clustering analysis. The distribution of organs or disease and the subclass of cancer immunotherapy were analyzed.ConclusionsIn this study, we classified the hot-spots of “tumor immunotherapy” into 6 categories and 8 aspects. Calculation and analysis revealed that the field of tumor immunotherapy shows a slight trend of polarization, and the immune checkpoint inhibitor PD1 blocker shows the greatest potential for future development.

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“…The mechanisms underlying the resistance of pancreatic cancer to the antitumor immune response have been extensively reviewed and are largely attributed to perturbations in immune surveillance, the process of immunoediting, and immune privilege [13,[59][60][61]. Although pancreatic cancer has been relatively resistant to singleagent checkpoint blockade when compared to more immune sensitive tumors, strategies for overcoming primary resistance to immunotherapy in pancreatic cancer are readily available from investigations in other solid tumor types focused on improving the antitumor efficacy of checkpoint blockade through combining various therapeutic modalities on a checkpoint inhibitor backbone [62][63][64].…”

Section: Mechanisms Of Immune Resistance and Rational Combination Strmentioning

confidence: 99%

Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single‐agent checkpoint blockade

Gong

Hendifar

Tuli

et al. 2018

Clinical & Translational Med

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Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell death protein 1 receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated protein 4. However, there is a growing body of preclinical evidence to support the rational combination of checkpoint inhibitors and various systemic therapies in pancreatic cancer. Furthermore, early clinical evidence has begun to support the feasibility and efficacy of checkpoint inhibitor-based combination therapy in advanced pancreatic cancer. Despite accumulating preclinical and clinical data, there remains several questions as to the optimal dosing and timing of administration of respective agents, toxicity of combination strategies, and mechanisms by which immune resistance to single-agent checkpoint blockade are overcome. Further development of biomarkers is also important in the advancement of combination systemic therapies incorporating checkpoint blockade in pancreatic cancer. Results from an impressive number of ongoing prospective clinical trials are eagerly anticipated and will seek to validate the viability of combination immuno-oncology strategies in pancreatic cancer.

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Immunotherapy for pancreatic cancer: A long and hopeful journey

Cited by 41 publications

References 94 publications

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer

Bibliometric Analysis of Tumor Immunotherapy Studies

Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single‐agent checkpoint blockade

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