Dataset Information

Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity.

ABSTRACT:

Background

T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor, dampens immune function. TIM-3 antagonists have entered the clinic.

Methods

We analyzed TIM-3 transcriptomic expression in 514 diverse cancers. Transcript abundance was normalized to internal housekeeping genes and ranked (0-100 percentile) to a reference population (735 tumors; 35 histologies [high≥75 percentile rank]). Ninety tumors (17.5%) demonstrated high TIM-3 expression.

Results

TIM-3 expression varied between and within tumor types. However, high TIM-3 expression was more common in pancreatic cancer (20/55 tumors, 36.4%; odds ratio, 95% confidence interval (pancreatic vs. other tumors) = 3.176 (1.733-5.818; p < 0.001, multivariate]). High TIM-3 also significantly and independently correlated with high PD-L1 (p = 0.014) and high CTLA-4 (p < 0.001) transcriptomic expression (multivariate).

Conclusions

These observations indicate that TIM-3 RNA expression is heterogeneous, but more common in pancreatic cancer and in tumors exploiting PD-L1 and CTLA-4 checkpoints. Clinical trials with patient selection for matched immune-targeted combinations may be warranted.

SUBMITTER: Lim J

PROVIDER: S-EPMC10807558 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity.

Lim Jungah J Kurzrock Razelle R Nishizaki Daisuke D Miyashita Hirotaka H Adashek Jacob J JJ Lee Suzanna S Pabla Sarabjot S Nesline Mary M Conroy Jeffrey M JM DePietro Paul P Lippman Scott M SM Kato Shumei S

Cancer medicine 20231222 1

<h4>Background</h4>T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor, dampens immune function. TIM-3 antagonists have entered the clinic.<h4>Methods</h4>We analyzed TIM-3 transcriptomic expression in 514 diverse cancers. Transcript abundance was normalized to internal housekeeping genes and ranked (0-100 percentile) to a reference population (735 tumors; 35 histologies [high≥75 percentile rank]). Ninety tumors (17.5%) demonstrated high TIM-3 expre ...[more]

PMID: 38132831

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Project description:BackgroundThe Veridex CellSearch is an FDA-approved technology for enumerating circulating tumor cells in blood samples of metastatic colorectal cancer mCRC) patients and has prognostic value. It is important to understand how counts of circulating tumor cells (CTCs), which are advocated to be tools for "liquid biopsy" of tumors, correlate with clinical and pathologic variables of significance in these patients. In this study, we have attempted to make such correlations along with evaluating how CTC counts change during the course of chemotherapy.Patients and methodsFollowing an IRB-approved protocol, blood samples were collected from 24 patients with mCRC along with relevant clinico-pathological data. Blood was collected at defined time-points both prior to as well as during the course of treatment with combination chemotherapy, and CTC counts were enumerated from 7.5 ml of blood.ResultsSeventeen out of 24 patients with mCRC showed a CTC count of 2 or less cells in 7.5 ml of blood at base-line assessment before chemotherapy while 7 patients showed 3 or more cells in 7.5 ml of blood at that point. A correlation was found between high carcino-embryonic antigen (CEA) levels and high CTC counts (P = 0.018) although it was also found that some patients had elevated CTCs without an elevated CEA. No correlation with the time interval between detection of primary tumor and appearance of secondary (metastatic) tumor(s) was found. CTC counts did not correlate with the presence of lung or liver metastases, i.e. a number of mCRC patients with lung or liver metastases had a count of zero CTCs at baseline. We also noted no correlation between CTC number and the status of KRAS or BRAF mutation. CTC counts dropped immediately after the start of chemotherapy in 11 out of 21 patients, and also reduced from the baseline at the end of chemotherapy in 5 out of 10 patients. Six of 7 patients who started with 3 or more CTCs in 7.5 ml at baseline also showed a final CTC reduction at the end of the therapy assessment.ConclusionsAnalysis of circulating tumor cells may be of use in monitoring response to therapy in mCRC, either in combination with CEA monitoring or alone when CTCs are elevated but CEA level is not.

Dataset Information

Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity.

Background

Methods

Results

Conclusions

Publications

Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity.

Similar Datasets

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