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The Diversity and Heterogeneity of TCR and BCR in Pan-Cancer

Yu-Bao Chen*, Bo Li1, Wen-Xiang Hu*, Li-Da Xu*, Hui-Xue Tang, Jing Zhang, Jin-Dan Guo

Introduction: With the development of the sequencing technology, RNA-seq is becoming more and more popular. The method of using RNA-seq technology to analyze the immune repertoire has the advantages of low sample demand, simple operation, and comprehensive information.

Methods: RNA-sequencing data were downloaded from SRA in NCBI, including 79 pairs of cancerous and adjacent noncancerous tissues samples of four representative cancer types, based on the literature, CutAdapt software was adopted to remove adapters, barcode bases, and low-quality bases. MiXCR software package was employed to extract immune repertoire receptor sequences.

Results: The RNA-seq data from public database were used to analyze and compare the TCR and BCR sequences of cancer and normal tissues in four types of cancers, including colon adenocarcinoma, lung adenocarcinoma, pancreatic adenocarcinoma and stomach adenocarcinoma. It was found that the clonal diversity of TCR among various types of cancer is different, and the variety of BCR between cancer tissues and healthy tissues is obvious. Based on the analysis of non-shared CDR3 sequences, the degree of the heterogeneity of TRB is different cancer types, different individuals with same cancer, cancer tissues and para-cancerous tissues of the same individual. Also, the correlation between the expression levels of the five main immune checkpoints genes and the count of TCR clones displayed various among different types of cancers.

Conclusion: Through the analysis of the immune repertoires in cancer tissues and adjacent non-cancer tissues of COAD, LUAD, PAAD and STAD, there were no significant differences found in TCR count and Shannon entropies within the same cancer type. But there are significant differences in TCR numbers and Shannon entropies among different cancer types. The results verify the advantage of RNA-seq analyzing in acquiring individual immune repertoire.