Controversial role of γδ T cells in pancreatic cancer

Shamohammadi, Fatemeh Nezhad; Yazdanifar, Mahboubeh; Oraei, Mona; Kazemi, Mohammad; Roohi, Azam; razavi, Seyedeh Mahya Shariat; Rezaei, Farhad; Parvizpour, Farzad; Karamlou, Yalda; Namdari, Haideh

doi:10.1016/j.intimp.2022.108895

Cited by 11 publications

(5 citation statements)

References 189 publications

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“…The formation of the immunosuppressive microenvironment of pancreatic cancer also seems to be related to the involvement of γδ T cells, which belong to the unconventional innate lymphocyte group and express T cell receptors (TCR) with γ and δ chains on their surface. 33 In normal pancreatic tissue or mice, the number of γδ T cells can be almost negligible, but PDAC patients compared with healthy patients, peripheral blood and PDAC tumor itself γδ T cells percentage increased. 34 Studies have shown that in pancreatic tumor stroma, γδ T cells are located near the PSC.…”

Section: Discussionmentioning

confidence: 94%

Research trends on immunotherapy for pancreatic cancer: A bibliometric analysis

Niu,

Jiang,

Fan

et al. 2023

Human Vaccines & Immunotherapeutics

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This study aims to summarize and visually analyze the current research status in pancreatic cancer immunotherapy during the past two decades by bibliometrics and explore the current research hotspots and future development directions. The literature related to pancreatic cancer immunotherapy from 2002 to 2021 was downloaded from the core database of the Web of Science. VOSviewer and CiteSpace software were used to visualize the included literature. A total of 2528 articles were included. In the past two decades, publications in the pancreatic cancer immunotherapy field have increased almost annually. As the country with the largest publications, the United States has various research institutions dedicated to pancreatic cancer immunotherapy. Jaffee EM and Zheng L from Johns Hopkins University and Vonderheide RH from the University of Pennsylvania have published the most articles in this field. The current research hotspots of pancreatic cancer immunotherapy include the tumor microenvironment, immune cells, immune checkpoint blockade, and combination therapy. The study of novel immunotherapies and combination therapy may become the primary focus of future research on pancreatic cancer immunotherapy. More prospective clinical studies with high evidence levels should be conducted.

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Section: Discussionmentioning

confidence: 94%

Research trends on immunotherapy for pancreatic cancer: A bibliometric analysis

Niu,

Jiang,

Fan

et al. 2023

Human Vaccines & Immunotherapeutics

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show abstract

“…Some immunohistochemical studies reported that high recruitment of TAMs, TANs, and FOXP3 + Tregs was associated with a worse prognosis in PDAC patients ( 151 , 152 ). However, similar to gastric carcinoma, infiltration of CD8 + T cells and CD20 + B cells is correlated with improved PFS in PDAC ( 152 , 153 ).…”

Section: Til Therapy For Treatment Of Human Solid Tumorsmentioning

confidence: 96%

Tumor-infiltrating lymphocytes for treatment of solid tumors: It takes two to tango?

et al. 2022

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Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small number and reduced activity limit their ability to overcome the tumor. Enhancement of TILs number and activity against tumors has been of interest for a long time. A lack of knowledge about the tumor microenvironment (TME) has limited success in primary TIL therapies. Although the advent of engineered T cells has revolutionized the immunotherapy methods of hematologic cancers, the heterogeneity of solid tumors warrants the application of TILs with a wide range of specificity. Recent advances in understanding TME, immune exhaustion, and immune checkpoints have paved the way for TIL therapy regimens. Nowadays, TIL therapy has regained attention as a safe personalized immunotherapy, and currently, several clinical trials are evaluating the efficacy of TIL therapy in patients who have failed conventional immunotherapies. Gaining favorable outcomes following TIL therapy of patients with metastatic melanoma, cervical cancer, ovarian cancer, and breast cancer has raised hope in patients with refractory solid tumors, too. Nevertheless, TIL therapy procedures face several challenges, such as high cost, timely expansion, and technical challenges in selecting and activating the cells. Herein, we reviewed the recent advances in the TIL therapy of solid tumors and discussed the challenges and perspectives.

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“…These unique antigen recognition properties endow γδ T cells with significant potential to maintain homeostasis 11 and execute anti-tumor immune responses 12,13 . They have been observed to infiltrate various tumor types, including rectal 14 , breast 15 , pancreatic 16 , kidney 17 , and colorectal cancers (CRC) 18,19 , exhibiting anti-tumoral cytotoxicity and regulatory effects in co-culture experiments in vitro [20][21][22][23][24][25][26][27][28][29] , in vivo animal models [30][31][32][33][34][35][36][37][38][39] , and functional assays on patient-derived γδ T cells 40,41 . γδ T cells can recognize and lyse cancer cells, which often exhibit MHC deficiencies or abnormalities 42 , in an MHC-unrestricted manner by producing classical cytotoxic molecules like granzyme B and perforin through direct contact via death receptor signaling 25,43,44 .…”

Section: Introduction γδ T Cells In Colorectal Cancer: An Introductionmentioning

confidence: 99%

Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

Ran,

Trapecar,

Brubaker

2024

Preprint

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Gamma delta (γδ) T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin-17 (IL-17) within the tumor microenvironment (TME) of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing (scRNA-seq) datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including Teff, TRM, Tpex, and Tex, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology.

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Controversial role of γδ T cells in pancreatic cancer

Cited by 11 publications

References 189 publications

Research trends on immunotherapy for pancreatic cancer: A bibliometric analysis

Research trends on immunotherapy for pancreatic cancer: A bibliometric analysis

Tumor-infiltrating lymphocytes for treatment of solid tumors: It takes two to tango?

Systematic Analysis of Human Colorectal Cancer scRNA-seq Revealed Limited Pro-tumoral IL-17 Production Potential in Gamma Delta T Cells

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