Dataset Information

T cell immunoglobulin and mucin-domain containing-3 in non-small cell lung cancer.

ABSTRACT:

Background

Immunotherapy has shown promising effect for non-small cell lung cancer (NSCLC) patients. Yet the biomarkers for predicting immunotherapy efficiency are still lacking.

Methods

We tested 139 surgical resected NSCLC primary tumor samples from Medical University of Gdansk, Poland, for T cell immunoglobulin and mucin-domain containing-3 (TIM-3) level by immunohistochemistry (IHC), analyzed the expression of TIM-3 protein on NSCLC tumor cells and tumor infiltrating lymphocytes (TILs).

Results

TIM-3 on TILs was correlated with programmed cell death protein-1 (PD-1) on TILs (correlation coefficient =0.346, P<0.001) and programmed cell death protein-ligand 1 (PD-L1) on TILs (correlation coefficient =0.313, P<0.001), PD-L1 level on tumor cells (correlation coefficient =0.255, P=0.002), TIM-3 level on tumor cells (correlation coefficient =0.262, P=0.002) and TIL percentage (correlation coefficient =0.172, P=0.043). TIM-3 level on tumor cells only had correlation with PD-L1 level (correlation coefficient =0.170, P=0.045). High level of TIM-3 on TILs indicated shorter recurrence-free survival (RFS) and overall survival (OS) (RFS 1.800 years, 95% CI, 1.230-2.370 vs. 0.870 years, 95% CI, 0.212-1.528, P=0.048) (OS 2.960 years, 95% CI, 2.268-3.652 vs. 1.080 years, 95% CI, 0.228-1.932, P=0.034).

Conclusions

TIM-3 is expressed on NSCLC tumor cells and TILs in all NSCLC pathological type. TIM-3 level on TILs had correlation with PD-1 and PD-L1 level. NSCLC patients with high TIM-3 level on TILs were more likely to have poor prognosis.

SUBMITTER: Jia K

PROVIDER: S-EPMC6976352 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

T cell immunoglobulin and mucin-domain containing-3 in non-small cell lung cancer.

Jia Keyi K He Yayi Y Dziadziuszko Rafal R Zhao Sha S Zhang Xiaoshen X Deng Juan J Wang Hao H Hirsch Fred R FR Zhou Caicun C Yu Hui H Zhang Liping L

Translational lung cancer research 20191201 6

<h4>Background</h4>Immunotherapy has shown promising effect for non-small cell lung cancer (NSCLC) patients. Yet the biomarkers for predicting immunotherapy efficiency are still lacking.<h4>Methods</h4>We tested 139 surgical resected NSCLC primary tumor samples from Medical University of Gdansk, Poland, for T cell immunoglobulin and mucin-domain containing-3 (TIM-3) level by immunohistochemistry (IHC), analyzed the expression of TIM-3 protein on NSCLC tumor cells and tumor infiltrating lymphocyt ...[more]

PMID: 32010568

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Project description:Targeting the interaction of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) and its ligands has been shown to reinstate antitumor immunity. In addition, the introduction of the LAIR-1 decoy protein, LAIR-2, sensitizes previously resistant lung tumors to programmed death-1 (PD-1) blockade, indicating the potential of LAIR-1 as an alternative marker for anti-PD-1 resistance in lung cancer. Here, we assessed LAIR-1 as compared with programmed death-ligand 1 (PD-L1) expression in various tumors, with a focus on non-small cell lung cancer (NSCLC) and its histologic subtypes using multiplexed quantitative immunofluorescence (mQIF) in 287 (discovery cohort) and 144 (validation cohort) patients with NSCLC. In addition, using multispectral imaging technology on mQIF images, we evaluated the localization of LAIR-1 on various cell types. We observed that CD14+, CD68+, and CD163+ monocytes and CK+ tumor cells predominantly expressed LAIR-1 more than other cell types. Furthermore, LAIR-1 expression in the tumor compartment was significantly higher in patients with lung adenocarcinoma (LUAD) than those with lung squamous cell carcinoma subtype (**, P = 0.003). Our results indicated that high tumor LAIR-1 expression in patients with LUAD is negatively associated with OS (overall survival, HR = 2.4; *, P = 0.02) highlighting its prognostic value in LUAD but not in other subtypes. The Pearson correlation between LAIR-1 and PD-L1 is 0.31; however, mutual exclusive staining pattern (i.e., several cases were positive for LAIR-1 and negative for PD-L1) was observed. Altogether, our data suggest that the combination therapy of anti-PD-1/PD-L1 with anti-LAIR-1 or the anti-LAIR-1 monotherapy alone may be promising cancer immunotherapeutic strategies.SignificanceThe spatial, quantitative assessment of LAIR-1 in NSCLC shows positive association of OS with high LAIR-1+/CD68+ cell densities and negative association of OS with high LAIR-1 expression in LUAD tumor subtype.

Dataset Information

T cell immunoglobulin and mucin-domain containing-3 in non-small cell lung cancer.

Background

Methods

Results

Conclusions

Publications

T cell immunoglobulin and mucin-domain containing-3 in non-small cell lung cancer.

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