Abstract PO-071: Pseudonormal morphology of adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells
Bibliographic record
Abstract
Abstract Objectives: Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer most frequently arising in the head and neck region. The ACC microenvironment exhibits low immunogenicity (low tumor infiltrating lymphocytes and dendritic cells). This scenario favours immune evasion and partially explains poor prognosis because of the activation of immune inhibitory proteins. Gipie is a hook-related protein, that is involved in protein trafficking. Gipie (HkRP3, encoded by CCDC88B) is associated with T cell maturation and inflammatory functions and target cell killing in natural killer (NK) cells. Gipie is present in ACC patient samples and cells. Therefore, we investigated proliferation, apoptosis, and morphologic changes caused by Gipie in oral and salivary gland cancer cells in presence of immune cells. Methods: We assayed UM-HACC-2A (adenoid cystic carcinoma), A-253 (mucoepidermoid carcinoma, MEC), SCC4, SCC9, SCC25, CAL27 (oral squamous cell carcinoma, OSCC), OKF6 (normal oral) cells cocultured with, NK-92 (natural killer), and Jurkat, Clone E6-1 (acute T cell leukemia) cells, to construct multiple salivary gland and oral cancer-immune cell co-culture models. Gipie silenced cancer cells (silencing maintained for 48 hours) in the cancer immune coculture models were compared with their unaltered subsets. Cancer-immune cells interactions were maintained for 16 hours. Overall three hundred thirty-six (336) co-culture models were used to determine apoptosis, immune activation, morphology, transmigration, and protein expression. Additionally, we performed targeted mass spectrometry analysis to identify changes in protein profiles. Results: ACC cells exhibited Pseudonormal morphology after interacting with immune cells in the 3D coculture model. Gipie-silenced ACC cells in coculture model transformed to “lymphoblast-like” morphology. Gipie-silenced ACC cells in co-culture model (n = 24) showed significant increase of apoptotic cells compared to unaltered ACC cells, lowering of T regulatory cells (FoxP3+/IL-2Rα+/CD25+) (n = 24), and increase of activated NK cells (NKp30+/IFN-γ+) (n = 24) with significantly higher release of granzyme (n = 12) and perforin (n = 12). Increased activation of immune cells (transmigration and fluorescence intensity) via 3D-z-stack images were observed in Gipie-silenced subsets (n = 24). MEC cells responses were significantly less compared to ACC in co-culture models followed by silencing of Gipie, while OSCC and OKF6 cell responses were negligible, under identical conditions. Conclusions: The presence of Gipie confers pseudonormal morphology to ACC cells thereby reducing immune attack. Thus, trafficking proteins may impact ACC cancer-immune cell interaction during conventional chemotherapy or monoclonal immunotherapy. Citation Format: Rajdeep Chakraborty, Charbel Darido, Giuseppe Palmisano, Arthur Chien, Aidan Tay, Thiri Zaw, Shoba Ranganathan. Pseudonormal morphology of adenoid cystic carcinoma cells subverts the antitumor reactivity of immune cells [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-071.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".