481P - Different gene mutation of colorectal cancer was tightly associated with various types of tumor immune microenvironment

Background

To better guide clinical applications of immune checkpoint inhibitors (ICI) and to select more CRC patients who is suitable for ICI therapy, evaluation of tumor immunity in the microenvironment (TIME) is an applicable direction. We evaluated characteristics of CRC TIME and try to establish association between gene mutation and TIME, therefore, to predict the TIME type of different CRC patient, furthermore, to judge CRC patients that suitable for ICI therapy.

Methods

Tumor tissue samples of 30 CRC patients were collected from December 2019, several kind of immune cells including CD8⁺ T cells, M1/M2 tumor associated macrophages (TAM) and two subtypes of NK cells infiltrated in the tumor tissue were be evaluate by multiple fluorescence immunohistochemistry (mICH), and expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, gene mutation were detected by means of next generation squesing (NGS). Chi-square test, Student’s test were used in IBM SPSS statistic 21.

Results

NGS detection shown that the main mutation among these samples were APC (14/20, 70%), KRAS (13/20, 65%), NRAS (7/20, 35%), PIK3CA (3/20, 15%), ARID1A (2/20, 10%), SMAD4 (4/20, 20%), FBXW7 (3/20, 15%) et al. All samples with negative PD-L1 expression. CD8⁺T cells, M1 and M2 TAM, CD56^bright NK and CD56^dim NK cells were found both in intratumoral region and tumor rim of these samples(n=20), further analysis revealed that TIME type was various among different gene mutation samples, in detail, more M1/M2 macrophages and CD56^bright NK cells infiltrated in sample with NRAS mutation than in NRAS wild type(p<0.05), more CD8⁺ T cells and M2 macrophages infiltrated in samples with SMAD4 mutation than SMAD4 wild type(p<0.05). While both more M2 macrophages and less CD8⁺T cells infiltrated in samples with PIK3CA mutation than wild type(p<0.05).

Conclusions

Almost all the CRC tumor immune macrophage with PD-L1 negative expression, imply exist other immune checkpoint in CRC tumor microenvironment, different mutation present different TIME type of CRC, suggest that different gene mutation could be used to predict the type of TIME, and therefore, to judge and determine the potential for immune checkpoint inhibitor therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Zhang, X. She, X. Shen, D. Huang: Full/Part-time employment: 3D Medicines Inc. All authors have declared no conflicts of interest.