Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells

Anadon, Carmen M.; Yu, Xiaoqing; Hänggi, Kay; Biswas, Subir; Chaurio, Ricardo A.; Martin, Alexandra; Payne, Kyle K.; Mandal, Gunjan; Innamarato, Patrick; Harro, Carly M.; Mine, Jessica A.; Sprenger, Kimberly B.; Cortina, Carla; Powers, John J.; Costich, Tara Lee; Perez, Bradford A.; Gatenbee, Chandler D.; Prabhakaran, Sandhya; Marchion, Douglas C.; Heemskerk, Mirjam H.M.; Curiel, Tyler J.; Anderson, Alexander R.A.; Rodríguez, Paulo C.; Conejo-García, José R.

doi:10.1016/j.ccell.2022.03.008

Cited by 75 publications

(45 citation statements)

References 84 publications

(90 reference statements)

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“… Assign T cell differentiation states to clusters using markers derived from Anadon et al. ( Anadon et al., 2022 ), following script deposited at GitHub https://github.com/xxy39/TRM_OV_sc/blob/main/DiffPlot.R . Calculate gene set activity scores for stemness, effector, proliferative, and exhaustive T cell differentiation states using R package AUCell ( Aibar et al., 2017 ).…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Description for analysis of single-cell omics data can also be found in Methods section of Anadon et al. ( Anadon et al., 2022 ).…”

Section: Data and Code Availabilitymentioning

confidence: 99%

“…We have also provided guidance for subsequent fluorescence-activated cell sorting (FACS), single-cell encapsulation, bioinformatics analysis, and troubleshooting. For complete details on the use and execution of this protocol, please refer to Anadon et al. (2022) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Anadon et al. (2022) .…”

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confidence: 99%

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Protocol for the isolation of CD8+ tumor-infiltrating lymphocytes from human tumors and their characterization by single-cell immune profiling and multiome

et al. 2022

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Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Description for analysis of single-cell omics data can also be found in Methods section of Anadon et al. ( Anadon et al., 2022 ).…”

Section: Data and Code Availabilitymentioning

confidence: 99%

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Anadon et al. (2022) .…”

mentioning

confidence: 99%

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Protocol for the isolation of CD8+ tumor-infiltrating lymphocytes from human tumors and their characterization by single-cell immune profiling and multiome

et al. 2022

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“…Highlevel IL-2 secreted by Th1 cells mediates the impairment of Tfh function through activating STAT5 signaling, whereas IL-6 secreted by DCs inversely prevents STAT5 from the combination of the IL-2rb locus (Hart and Laufer, 2022). Astoundingly, TGF-β in humans plays a protective role for Tfh cells, which activates STAT3 and STAT4 by interacting with IL-12 and IL-23, and silences genomic organizer SATB1 to aid Tfh cell differentiation (Kurata et al, 2021;Chaurio et al, 2022;Schmidleithner and Feuerer, 2022). However, it is a negative regulator in mice, and using TGF-β inhibitors reduces Tfh accumulation in the tumor sites (McCarron and Marie, 2014;Niogret et al, 2021).…”

Section: Follicular Helper T Cellsmentioning

confidence: 99%

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Wang

Zhuling³

et al. 2022

Front. Genet.

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In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

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Intratumoral CD103⁺CD8⁺ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma

Ren,

Lan,

et al. 2023

Cancer Communications

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BackgroundImmune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC.MethodsWe performed combined single‐cell RNA sequencing (scRNA‐seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI‐treated HNSCC patients to identify a new tumor‐infiltrating cell (TIL) subtype, CD103+CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+CD8+ TILs population was examined by performing cell‐cell interaction analysis of the scRNA‐seq data and spatial analysis of the mIHC images.ResultsWe established intratumoral CD103+CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA‐seq results indicated that the population of CD103+CD8+ TILs was dramatically increased in the responders of NACI‐treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+CD8+ TILs were tumor‐reactive T cells, while programmed cell death protein‐1 (PD‐1) blockade enhanced CD103+CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2‐positive (TREM2+) macrophages might enhance the population of CD103+CD8+ TILs and facilitate antitumor immunity during NACI treatment.ConclusionsOur study highlights the impact of intratumoral CD103+CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

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Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells

Cited by 75 publications

References 84 publications

Protocol for the isolation of CD8+ tumor-infiltrating lymphocytes from human tumors and their characterization by single-cell immune profiling and multiome

Protocol for the isolation of CD8+ tumor-infiltrating lymphocytes from human tumors and their characterization by single-cell immune profiling and multiome

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Intratumoral CD103⁺CD8⁺ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma

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Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells

Cited by 75 publications

References 84 publications

Protocol for the isolation of CD8+ tumor-infiltrating lymphocytes from human tumors and their characterization by single-cell immune profiling and multiome

Protocol for the isolation of CD8+ tumor-infiltrating lymphocytes from human tumors and their characterization by single-cell immune profiling and multiome

The soldiers needed to be awakened: Tumor-infiltrating immune cells

Intratumoral CD103+CD8+ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma

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Intratumoral CD103⁺CD8⁺ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma