Abstract 1489: Basal cell carcinomas express functional indoleamine 2,3-dioxygenase (IDO) which may confer immunoprotection
Bibliographic record
Abstract
Abstract Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Besides genetic alterations, abrogation of host immune defense has been suggested to enable tumor growth. Cancer cells may express factors that confer resistance to inflammatory cell mediated activity and may actively suppress immune targeting mechanisms. BCCs can derive from hair follicle bulge region keratinocytes; a structure which exhibits elements of immune privilege (IP). As such, BCCs may also exhibit immunoprotective characteristics during tumorigenesis. Indoleamine 2,3-dioxygenase (IDO) suppresses T lymphocyte proliferation via tryptophan catabolism in the kynurenine pathway. IDO is used as an immune subversion strategy by several types of cancer such as ovarian carcinomas. Expression of IDO has also been identified in hair follicle keratinocytes. Taken together, we hypothesized that IDO might have an impact on the putative IP of BCCs. In a preliminary study, we identified increased expression of mRNA in BCCs for several IP related factors. In this study, real-time RT-PCR identified significant upregulation of IDO-1 and IDO-2 (12.5- and 19.1-fold change respectively) in human nodular BCCs (n=10) as compared to non-lesional skin epithelium tissues (n=10). Dual label immunohistochemistry revealed co-localization of IDO and keratin 17 (K17), which is a BCC keratinocyte marker, in human BCC tissues (n=5). Western blot detected IDO (42kDa) and a 30kDa IDO isoform in BCC tissues (n = 6). Activity of IDO was shown by significantly increased production of L-kynurenine in the conditioned medium from cell cultures. CXCL11 has recently been shown to be a supplement required for the survival and growth of primary human BCC cells in culture. Addition of CXCL11 to primary BCC cell cultures in increased concentrations promoted increased L-kynurenine in a dose dependent manner. However, there was no significant increase in L-kynurenine production by normal primary human keratinocytes under CXCL11 treatment. In conclusion, of several differentially expressed genes associated with IP, mRNA for IDO was identified with significantly increased expression. The co-expression of the peptide with K17, as well as the IDO-mediated L-kynurenine production in human BCC cell cultures, provides further evidence of functional IDO synthesis by BCCs during their growth. The results suggest that BCCs may exhibit IP characteristics through IDO production and induction of a local collapse of such IP systems in BCC tumors may be a novel strategy for promoting BCC regression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1489.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.003 | 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".