Phenotypic analysis of tumor-infiltrating lymphocytes from non-small cell lung cancer and their potential application for adoptive cell therapy

Abstract

Aim

Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) has demonstrated clinical benefits in metastatic melanoma treatment. However, the clinical application of TILs produced by a widely used standard protocol from non-small cell lung cancer (NSCLC) can be quite challenging because of the limited clinical benefits. A comprehensive phenotypic knowledge of TILs obtained from NSCLC is important for the development and improvement of personalized TIL therapy for NSCLC patients.

Methods

In this study, we successfully expanded TILs from 141 NSCLC tissues which can be used in clinical ACT after expansion by a rapid expansion protocol (REP).

Results

Our study indicates that the clinicopathological characteristics of patients have considerable impacts on the phenotype of in vitro TIL culture products. Different culture conditions are necessary for patients with different clinical features. Specific manipulations before REP expansion are required depending on the different phenotypes of TIL cultures (e.g. depletion of immune-suppressive γδT cells). With these optimizations, next-generation TIL therapy may become a treatment alternative for NSCLC patients in the future.

Keywords:

• Adoptive cell therapy
• tumor-infiltrating lymphocytes
• phenotypic analysis
• clinical characteristics
• non-small cell lung cancer

Disclosure statement

The authors declare no potential conflicts of interest.

Additional information

Funding

This

work was supported by the [Shenzhen Basic Research Program] under Grant [number JCYJ20170412102821202 and JCYJ20180507182902330]; [Shenzhen Peacock Plan] under Grant [number KQTD20130416114522736]; [Special Funds for Dapeng New District Industry Development] under Grant [number KY20150116, KY20160309, KY20170203, KY20180105, and KY20180214]; China Postdoctoral Science Foundation [2019M652849]; Natural Science Foundation of Guangdong Province [2019A1515010629].