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Soluble form of tim3 in immune checkpoint blockade therapy resistance

A form, dissolvable technology for advancing advances in biomedicine and molecular biology

Active Publication Date: 2022-06-24
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, whether sTim-3 may be a biomarker for PD-1 blockade therapy in tumor patients and whether it plays a role in PD-1 blockade therapy in tumor patients has not been reported yet.

Method used

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  • Soluble form of tim3 in immune checkpoint blockade therapy resistance
  • Soluble form of tim3 in immune checkpoint blockade therapy resistance
  • Soluble form of tim3 in immune checkpoint blockade therapy resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0081] experimental method

[0082] 1. Specimen processing method

[0083] Anticoagulant samples were centrifuged at 1200r / 5min to harvest serum and cell pellet respectively. Serum was used to detect sTim-3 by ELISA. Cell pellet was lysed twice with erythrocyte lysate to harvest peripheral blood immune cells. After adding trizol, RNA was extracted and reversed. recorded into cDNA.

[0084] 2. sTim-3 detection

[0085] Take out the microplate from the kit, add 100 μl RD1W to each well, then add 50 μl sample to each well, place it on a microplate shaker and incubate for 1 h at room temperature, discard the supernatant, add 400 μl washing solution to each well to wash, repeat 4 times, add 200 μl of Tim-3 antibody to each well, incubate at room temperature for 1 h on a microplate shaker, repeat the plate washing step, add 200 μl of substrate, incubate at room temperature for 30 min in the dark, add 50 μl of stop solution, and enzyme within 30 min The absorbance was measured by ...

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Abstract

The invention provides the application of a soluble form of Tim3 in immune checkpoint blockade treatment resistance, and belongs to the technical fields of biomedicine and molecular biology. The present invention has found through research that the soluble form of Tim3 is not only significantly up-regulated in NSCLC that does not respond to PD-1 blockade therapy, but also shows a higher serum level in cholangiocarcinoma, which has been reported to be resistant to PD-1 Blocking therapy has strong resistance. Importantly, the present invention found that sTim-3 induced resistance to PD-1 antibody blockade therapy in a mouse model of ICC and promoted tumor progression by suppressing T cell function in a CEACAM1-dependent manner. Therefore, human sTim‑3 can be used as a candidate biomarker for tumor progression and resistance to PD‑1 blockade therapy, and a new mechanism for Tim‑3-mediated immunosuppression and resistance to PD‑1 blockade therapy in the tumor environment was proposed , has good practical application value.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and molecular biology, and particularly relates to the application of soluble form Tim3 in immune checkpoint blockade therapy resistance. Background technique [0002] The information disclosed in this Background of the Invention is only for enhancement of understanding of the general background of the invention and should not necessarily be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person of ordinary skill in the art. [0003] Immune cells, especially T cells, are often depleted in the tumor microenvironment. Exhausted T cells show high expression of multiple inhibitory receptors (immune checkpoints), such as programmed cell death receptor 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), and the gradual progression of effector function. loss and reduced ability to kill tumor cells. Immune checkpoint blockade (IC...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N33/574A61K45/00A61P35/00
CPCG01N33/57488G01N33/57423G01N33/57419G01N33/57446G01N33/57438A61K45/00A61P35/00G01N2800/52G01N2500/20
Inventor 李春阳马春红陈朝佳彭加丽马帅雅高立芬梁晓红
Owner SHANDONG UNIV
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