Abstract 1361: Crosstalk between peripherally expanded T cells and Tfh-like cells in shaping effector functions of CD8 T cells in ovarian cancer
Bibliographic record
Abstract
Abstract Background: Immune checkpoint blockade (ICB) of PD-1 and/or CTLA-4 can induce long-lasting clinical responses in several neoplasias. However, despite the successful response in some cancer, it is still ineffective for other malignant lesions such as ovarian cancer. Studies on T cell dynamics demonstrated that antitumor immune response from ICB is mediated by clonal replacement of CD8 T cells. Moreover, the presence of clones expanded in both tumor and peripheral tissue, also called dual-expanded, can predict response to ICB. To understand T cell dynamics in ovarian cancer, we characterized intratumoral and peripheral immune cells by single-cell transcriptome and TCR-sequencing. Methods and results: Using the 5’ Chromium assay (10X Genomics) on CD45+ cells isolated from 5 naïve-treatment patients undergoing cytoreductive surgery, we identified T cell states and classified clones by location (blood or tumor) and expansion pattern. In addition, the data revealed that clones expanded within the tumor were terminally exhausted (upregulation of PDCD1, HAVCR2, CTLA4, ENTPD1, and CXCL13 genes), while dual-expanded clones (expanded in blood and tumor) upregulated genes associated with the cytotoxic function of CD8 T cells, such as granzymes (GZMA and GZMB) and perforin (PRF1). Considering the importance of dual-expanded clones in antitumor immune response, we interrogated the cellular interactions they encountered in the tumor microenvironment. Using the tool NicheNet we identified IL21 as one of the top ligands mediating the interaction between dual-expanded clones and T follicular helper-like CD4+ cells (Tfh-like cells). Interestingly, the gene signature of Tfh-like cells showed that besides dual-expanded clones, these cells might attract other immune cells through CXCL13 and oxysterol metabolites. We identified B cells and plasmacytoid dendritic cells (pDCs) as the major cell types recruited by the CXCL13-CXCR5 axis and oxysterol-GPR183, respectively. Additionally, memory-like CD8 T cells were found to express GPR183, suggesting that a gradient of oxysterol might recruit them to a region defined by Tfh-like cells. Conclusions: Taken together, our study provides insights into additional functions of Tfh-like cells in the recruitment of immune cells through oxysterol gradient. A better understanding of the T cell dynamics and antitumor immune response can provide potential development of novel immunotherapy for the treatment of ovarian cancer. Citation Format: Mayra Carneiro, Cheng Zhao, Paméla Thébault, Yacine Bareche, Kurosh Rahimi, Jean-François Cailhier, Anne-Marie Mes-Masson, John Stagg, Sophie Petropoulos, Réjean Lapointe. Crosstalk between peripherally expanded T cells and Tfh-like cells in shaping effector functions of CD8 T cells in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1361.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".