Intratumoral heterogeneity may become another important marker of lung cancer immunotherapy

The oncology journal "Molecular Cancer" published online the latest research results of the team of Professor Zhang Li, the chief expert on lung cancer from the Cancer Center of Sun Yat-sen University: bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">intratumoral heterogeneity (ITH) can be used as lung cancer to accept anti-PD-1/PD-L1 Predictive bioon.
com/biomarkers/list-2.
html" target="_blank">biomarkers for monoclonal antibody treatment .
This is the first study based on a single-point sampling method to prove the correlation between intratumoral heterogeneity of lung cancer in the Chinese population and immunotherapy.

In the past ten years, immune checkpoint inhibitors (ICIs) have made significant progress in the clinical treatment of tumors.
However, immunotherapy also has problems such as low proportion of effective population, drug resistance, super progress, etc.
Only about 20% of patients can benefit from ICIs monotherapy.
Therefore, there is an urgent need to find effective biomarkers to screen the benefiting population.
.
The currently widely accepted bioon.
com/biomarkers/list-2.
html" target="_blank">biomarkers (such as PD-L1, TMB) are not perfect enough, and some patients with low TMB or PD-L1 negative can still benefit from immune checkpoint inhibitors.
In recent years, intratumoral heterogeneity (ITH) has received more and more attention and is considered to be one of the main factors affecting tumor immune resistance.
As early as 2019, Professor Zhang Zhang’s team published a study on the intratumoral heterogeneity of lung cancer in Molecular Cancer.
Through a multi-point sampling method, it was found that lung cancer patients with EGFR mutations had a higher level of intratumoral heterogeneity.
Intratumoral heterogeneity is one of the reasons for the poor efficacy of immunotherapy in patients with EGFR-mutant lung cancer.
However, the feasibility of this multi-point sampling method to calculate intratumoral heterogeneity is poor, and it is difficult to apply and popularize in actual clinical practice.
In order to solve this clinical problem and enable more patients to benefit from treatment, Professor Zhang’s team optimized the algorithm of intratumoral heterogeneity and verified that bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">intratumoral heterogeneity based on single-point sampling is different.
The feasibility of predicting the efficacy of immunotherapy in cancer species.

The main innovations of this breakthrough research are:

1.
Feasibility: A single point sampling can estimate the degree of overall bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">intratumoral heterogeneity of the patient

The overall intra-tumor heterogeneity calculated based on the new algorithm can represent the intra-tumor heterogeneity of multi-point sampling to a large extent, and is highly correlated with the median intra-tumor heterogeneity of the patient's multi-point sampling, with a coefficient of up to 0.
96, verify the bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor clinical heterogeneity within the feasibility analysis of samples from a single point to multi-point sampling.

2.
Independence: bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">intratumoral heterogeneity alone or in combination with TMB can predict efficacy

Patients with ITH-L have a longer survival period.
In addition, the heterogeneity distribution within the tumor is not related to TMB, and can be considered as two independent indicators.
When combined with TMB, bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">intratumoral heterogeneity can further distinguish the two groups with good curative effect and poor curative effect among TMB-L patients.

3.
Compatibility: It can also be tested on large panel platforms with lower cost and higher throughput

In the process of verifying intra-tumor heterogeneity indicators to predict the effectiveness of immunotherapy, the MSKCC pan-cancer data set, POPLAR and OAK data sets are used, which are all based on the data of Foundation Medicine's tissue and blood panel testing.
This also shows from the side that intra- bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor heterogeneity is not only effective in WES testing, but can also be predicted in panel data, realizing the conversion of high-cost WES testing to low-cost, clinically accessible multi-gene panel testing.

4.
Non-invasiveness: to achieve compatibility of tissue testing and peripheral blood testing

With the development of tumor detection technology, the importance of liquid biopsy has been recognized more and more, especially for circulating tumor DNA (ctDNA) in peripheral blood.
In order to explore whether the predictive effect of intratumoral heterogeneity can be applied to ctDNA data, the research team also introduced two immunotherapy cohorts, POPLAR and OAK.
The results found that the discovery of bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">intratumoral heterogeneity can effectively distinguish benefiting groups from the bTMB-L group, suggesting that in the future, it is hoped that ctDNA detection, an economic, universal and non-invasive method, can be used to promote and apply ITH, and further reduce the burden on patients.

5.
Versatility: applicable to different tumor types

Using MSKCC's pan-cancer species data for verification, it is found that ITH analysis is not only applicable to lung cancer, but also to multiple tumor types, especially low TMB population and tumor types with poor TMB prediction value, such as nasopharyngeal carcinoma and hyaline kidney Cell carcinoma, etc.
, are versatile.

This study is the first study to verify the predictive value of intratumoral heterogeneity for immunotherapy efficacy in multiple tumor species, and it is also the first to find that there is a relationship between the median intratumoral heterogeneity and immunotherapy efficacy at the pan-cancer species level.
Correlation, and innovatively use data from different detection methods and sample sources to analyze the feasibility of intratumoral heterogeneity.
The research team first used the optimized intra-tumor heterogeneity algorithm to successfully achieve a single-point sampling to estimate the patient's overall intra-tumor heterogeneity degree, making intra-tumor heterogeneity feasible for practical clinical application and promotion.
It is further discovered that intratumoral heterogeneity is a potential immunotherapy bioon.
com/biomarkers/list-2.
html" target="_blank">biomarker , which can predict the efficacy of patients with advanced NSCLC, and even predict the efficacy of patients with other tumor types receiving ICI therapy.
Its performance is most prominent in people with low TMB, suggesting that the comprehensive assessment of intratumoral heterogeneity and TMB can further expand the population with advantages in ICI treatment.
What's more gratifying is that intratumoral heterogeneity is not only applicable to different tumor types, but can also be expressed in tumor tissues and peripheral blood (ctDNA), and is not limited to the method of detection (WES or panel is both).
versatility and compatibility exhibited bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor potential advantages in the clinical application of immunotherapy heterogeneity as a biomarker.
(bioon.
com" target="_blank">Bioon.
com)