Tissue Resident CD8 Memory T Cell Responses in Cancer and Autoimmunity

Molodtsov, Aleksey; Turk, Mary Jo

doi:10.3389/fimmu.2018.02810

Cited by 81 publications

(65 citation statements)

References 163 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trm cells produce higher amounts of cytokines than their circulating counterparts and provide enhanced local immunity in response to infection (12,13). CD8 þ Trm cells are associated with antitumor immune responses (14,15). The presence of Trm cells correlates with improved prognosis in patients with cancer (16,17).…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid Oxidation Controls CD8+ Tissue-Resident Memory T-cell Survival in Gastric Adenocarcinoma

Lin

Zhang

Yuan

et al. 2020

Cancer Immunology Research

143

118

View full text Add to dashboard Cite

The success of checkpoint inhibitors in cancer treatment is associated with the infiltration of tissue-resident memory T (Trm) cells. In this study, we found that about 30% of tumorinfiltrating lymphocytes (TIL) in the tumor microenvironment of gastric adenocarcinoma were CD69 þ CD103 þ Trm cells. Trm cells were low in patients with metastasis, and the presence of Trm cells was associated with better prognosis in patients with gastric adenocarcinoma. Trm cells expressed high PD-1, TIGIT, and CD39 and represented tumor-reactive TILs. Instead of utilizing glucose, Trm cells relied on fatty acid oxidation for cell survival. Deprivation of fatty acid resulted in Trm cell death. In a tumor cell-T-cell coculture system, gastric adenocarcinoma cells outcompeted Trm cells for lipid uptake and induced Trm cell death. Targeting PD-L1 decreased fatty acid binding protein (Fabp) 4 and Fabp5 expression in tumor cells of gastric adenocarcinoma. In contrast, the blockade of PD-L1 increased Fabp4/5 expression in Trm cells, promoting lipid uptake by Trm cells and resulting in better survival of Trm cells in vitro and in vivo. PD-L1 blockade unleashed Trm cells specifically in the patientderived xenograft (PDX) mice. PDX mice that did not respond to PD-L1 blockade had less Trm cells than responders. Together, these data demonstrated that Trm cells represent a subset of TILs in the antitumor immune response and that metabolic reprogramming could be a promising way to prolong the longevity of Trm cells and enhance antitumor immunity in gastric adenocarcinoma.

show abstract

Section: Introductionmentioning

confidence: 99%

Fatty Acid Oxidation Controls CD8+ Tissue-Resident Memory T-cell Survival in Gastric Adenocarcinoma

Lin

Zhang

Yuan

et al. 2020

Cancer Immunology Research

143

118

View full text Add to dashboard Cite

show abstract

“…T he induction of CD8 tissue-resident memory T cells (Trm) in the lung following respiratory infection is an integral component of front-line mucosal defense against future pathogen exposure (1-5). However, the mechanism of lung Trm differentiation and commitment remains unclear (1,2,6,7). It was recently demonstrated that the TNFR superfamily member 4-1BB provides a critical signal for the establishment of influenzaspecific lung-resident memory T cells, as measured at day 30 postinfection in the lung (8).…”

mentioning

confidence: 99%

4-1BB Regulates Effector CD8 T Cell Accumulation in the Lung Tissue through a TRAF1-, mTOR-, and Antigen-Dependent Mechanism to Enhance Tissue-Resident Memory T Cell Formation during Respiratory Influenza Infection

Zhou

Batista

Watts

2019

The Journal of Immunology

View full text Add to dashboard Cite

The TNFR superfamily member 4-1BB is important in the establishment of tissue-resident memory T cells (Trm) in the lung tissue following influenza infection. Moreover, supraphysiological boosting of 4-1BB in the airways during the boost phase of a prime-boost immunization regimen increases the long-lived Trm population, correlating with increased protection against heterotypic challenge. However, little is known about how 4-1BB contributes to the establishment of the lung Trm population. In this study, we show that effects of 4-1BB on lung Trm accumulation are already apparent at the effector stage, suggesting that the major role of 4-1BB in Trm formation is to allow persistence of CD8 T effector cells in the lung as they transition to Trm. Using supraphysiological stimulation of 4-1BB in the boost phase of a prime-boost immunization, we show that the effect of 4-1BB on Trm generation requires local delivery of both Ag and costimulation, is inhibited by rapamycin treatment during secondary CD8 effector T cell expansion, and is dependent on the signaling adaptor TRAF1. The decrease in lung Trm following early rapamycin treatment is accompanied by increased circulating memory T cells, as well as fewer effectors, suggesting a role for mammalian target of rapamycin (mTOR) in the formation of Trm through effects on the accumulation of effector precursors. Taken together, these data point to an important role for 4-1BB, TRAF1, and mTOR in the persistence of CD8 effector T cells in the lung parenchyma, thereby allowing the transition to Trm.

show abstract

“…Among TILs, T resident-memory (T RM ) cells are permanent tissue-resident T cells able to mount an immune reaction; they've been proposed to be key determinants in the magnitude of antitumor immune responses, and their presence in different human cancers correlates with survival (329)(330)(331)(332)(333)(334)(335)(336). It is tempting to assume that the induction and/or manipulation of this T cell subset might improve anti-tumor immunity and disease control.…”

Section: Generating Genetically Engineered T Resident-memory Cellsmentioning

confidence: 99%

TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals

et al. 2020

View full text Add to dashboard Cite

Adoptive T cell therapy (ACT) is a rapidly evolving therapeutic approach designed to harness T cell specificity and function to fight diseases. Based on the evidence that T lymphocytes can mediate a potent anti-tumor response, initially ACT solely relied on the isolation, in vitro expansion, and infusion of tumor-infiltrating or circulating tumor-specific T cells. Although effective in a subset of cases, in the first ACT clinical trials several patients experienced disease progression, in some cases after temporary disease control. This evidence prompted researchers to improve ACT products by taking advantage of the continuously evolving gene engineering field and by improving manufacturing protocols, to enable the generation of effective and long-term persisting tumor-specific T cell products. Despite recent advances, several challenges, including prioritization of antigen targets, identification, and optimization of tumor-specific T cell receptors, in the development of tools enabling T cells to counteract the immunosuppressive tumor microenvironment, still need to be faced. This review aims at summarizing the major achievements, hurdles and possible solutions designed to improve the ACT efficacy and safety profile in the context of liquid and solid tumors.

show abstract

Tissue Resident CD8 Memory T Cell Responses in Cancer and Autoimmunity

Cited by 81 publications

References 163 publications

Fatty Acid Oxidation Controls CD8+ Tissue-Resident Memory T-cell Survival in Gastric Adenocarcinoma

Fatty Acid Oxidation Controls CD8+ Tissue-Resident Memory T-cell Survival in Gastric Adenocarcinoma

4-1BB Regulates Effector CD8 T Cell Accumulation in the Lung Tissue through a TRAF1-, mTOR-, and Antigen-Dependent Mechanism to Enhance Tissue-Resident Memory T Cell Formation during Respiratory Influenza Infection

TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals

Contact Info

Product

Resources

About