Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer

Peng, Hui; James, Cyan; Cullinan, Darren R.; Hogg, Graham D.; Mudd, Jacqueline; Zuo, Chong; Takchi, Rony; Liu, Jingxia; DeNardo, David G.; Fields, Ryan C.; Gillanders, William E.; Goedegebuure, S. Peter; Hawkins, William G.

doi:10.1158/1078-0432.ccr-21-0998

Cited by 40 publications

(27 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may explain our results, in which activation of CD8 + T cells, as well as the high abundance of memory T cells, significantly prolongs the OS time of CC patients. Surprisingly, the results showed that high Treg infiltration was significantly associated with good prognosis of patients, which was quite opposite to the phenomenon widely reported thus far ( Banerjee et al, 2021 ; Dahlhoff et al, 2021 ; Peng et al, 2021 ). In previous reports, little literature has mentioned that Treg can participate in the immune process as a protective factor.…”

Section: Discussioncontrasting

confidence: 98%

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Wang

Ding

Cui

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells’ infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.

show abstract

Section: Discussioncontrasting

confidence: 98%

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Wang

Ding

Cui

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…In contrast, chemotherapy can also induce immunosuppressive effects, including the increase in tumor-promoting MDSCs [ 41 , 42 , 43 ]. In addition, it has been reported that neoadjuvant chemotherapy results in an increased frequency of PDAC-infiltrating CD4 + and CD8 + T cells, while the density of Tregs and MDSCs decreases [ 44 , 45 , 46 , 47 ]. Following these findings, we explored the influence of neoadjuvant chemotherapy on the level of PDAC-associated DCs.…”

Section: Resultsmentioning

confidence: 99%

Clinical Significance of Tumor-Infiltrating Conventional and Plasmacytoid Dendritic Cells in Pancreatic Ductal Adenocarcinoma

Plesca

Benešová

Beer

et al. 2022

Cancers

View full text Add to dashboard Cite

Dendritic cells (DCs) play a key role in the orchestration of antitumor immunity. Activated DCs efficiently enhance antitumor effects mediated by natural killer cells and T lymphocytes. Conversely, tolerogenic DCs essentially contribute to an immunosuppressive tumor microenvironment. Thus, DCs can profoundly influence tumor progression and clinical outcome of tumor patients. To gain novel insights into the role of human DCs in pancreatic ductal adenocarcinoma (PDAC), we explored the frequency, spatial organization, and clinical significance of conventional DCs type 1 (cDC1s) and type 2 (cDC2s) and plasmacytoid DCs (pDCs) in primary PDAC tissues. A higher density of whole tumor area (WTA)- and tumor stroma (TS)-infiltrating cDC1s was significantly associated with better disease-free survival (DFS). In addition, an increased frequency of intraepithelial tumor-infiltrating cDC2s was linked to better DFS and overall survival (OS). Furthermore, an increased density of WTA- and TS-infiltrating pDCs tended to improve DFS. Moreover, a higher frequency of WTA- and TS-infiltrating cDC1s and pDCs emerged as an independent prognostic factor for better DFS and OS. These findings indicate that tumor-infiltrating DCs can significantly influence the clinical outcome of PDAC patients and may contribute to the design of novel treatment options that target PDAC-infiltrating DCs.

show abstract

“…In human PDAC patients, higher plasma concentrations of CXCL9 and CXCL10 in patients also correlate with improved overall survival (Qian et al, 2019). Abundance of CXCR3-expressing T cell infiltration has been shown to correlate with better responses to FOLFIRINOX (Peng et al, 2021). In mouse colorectal models, CXCR3 signaling was also shown to be required for responsivity to PD1 blockade (Chow et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Notch signaling in tumor vasculature programs cancer-associated fibroblasts to suppress anti-tumor immunity

Zhu

Xiang

Brulois

et al. 2022

Preprint

View full text Add to dashboard Cite

Scarcity of tumor-infiltrating T cells poses significant challenges to cancer treatment, but mechanisms that regulate T cell recruitment into the tumor microenvironment are unclear. Here we ask if the endothelial lining of tumor vasculature suppresses T cell infiltration. Using mouse pancreatic ductal adenocarcinoma models, we found that Notch signaling in endothelial cells (ECs) inhibits the pro-inflammatory functions of cancer-associated fibroblasts (CAFs) and prevents CAFs from secreting CXCL10, a chemokine that recruits anti-tumor T cells via its receptor CXCR3. Abrogation of canonical Notch signaling in ECs reprogrammed the phenotype of CAFs from myofibroblasts into pro-inflammatory fibroblasts, unleashed interferon gamma (IFNg) responses in the tumor, and stimulated CXCL10/CXCR3-mediated recruitment of T cells to inhibit tumor growth. Collectively, these data uncover an important role of endothelial Notch signaling in shaping the tumor immune microenvironment, and suggest the potential of targeting EC-CAF crosstalk as an approach to enhance anti-tumor immunity in immunologically cold tumors.

show abstract

Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer

Cited by 40 publications

References 52 publications

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Clinical Significance of Tumor-Infiltrating Conventional and Plasmacytoid Dendritic Cells in Pancreatic Ductal Adenocarcinoma

Notch signaling in tumor vasculature programs cancer-associated fibroblasts to suppress anti-tumor immunity

Contact Info

Product

Resources

About