Open Access

Comprehensive investigation of T and B cell receptor repertoires in an MC38 tumor model following murine anti‑PD‑1 administration

  • Authors:
    • Lu Zhang
    • I‑Ming Wang
    • Nicolas Solban
    • Razvan Cristescu
    • Gefei Zeng
    • Brian Long
  • View Affiliations

  • Published online on: May 22, 2020     https://doi.org/10.3892/mmr.2020.11169
  • Pages: 975-985
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The MC38 (derived from carcinogen‑induced colon adenocarcinoma) tumor model is sensitive to anti‑programmed cell death‑1 (anti-PD‑1) treatment. However, there is no comprehensive description of the T and B cell receptor (TCR, BCR) repertoires of the MC38 tumor model following anti‑PD‑1 treatment, an improved understanding of which is highly important in the development of anti‑PD‑1 immunotherapy. The present study analyzed the TCR and BCR repertoires of three types of tissue, including tumor, spleen and tumor draining lymph node (DLN) from 20 MC38 syngeneic mice receiving murine anti‑PD‑1 (mDX400) treatment or mouse immunoglobulin G1 (mIgG1) control treatment. To obtain enough tissues for high‑throughput sequencing, samples were collected on day 8 after the start of initial treatment. The usage frequencies of seven TCR β chain (TRB) V genes and one TRBJ gene were significantly different between mDX400‑ and mIgG1‑group tumors. TCR repertoire diversity was significantly lower in mDX400‑group tumors compared with mIgG1‑group tumors, with the top 10 most frequent TCR clonotypes notably expanded in mDX400‑group tumors. In addition, the proportion of high‑frequency TCR clonotypes from mDX400‑group tumors that were also present both in the DLN and spleen was significantly higher than that in mIgG1‑group tumors. Among the highly expanded TCR clonotypes, one TCR clonotype was consistently expanded in >50% of the mDX400‑group tumors compared with mIgG1‑group tumors. Similarly, one BCR clonal family was highly expanded in >50% of mDX400‑group tumor samples. The consistently expanded TCR and BCR clones were co‑expanded in 29% of mDX400‑group tumors. Moreover, mutation rates of immunoglobulin heavy chain sequences in the spleen within complementarity determining region 2 and framework region 3 were significantly higher in the mDX400 group than in the mIgG1 group. The findings of this study may contribute to an improved understanding of the molecular mechanisms of anti‑PD‑1 treatment.

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August-2020
Volume 22 Issue 2

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APA
Zhang, L., Wang, I., Solban, N., Cristescu, R., Zeng, G., & Long, B. (2020). Comprehensive investigation of T and B cell receptor repertoires in an MC38 tumor model following murine anti‑PD‑1 administration. Molecular Medicine Reports, 22, 975-985. https://doi.org/10.3892/mmr.2020.11169
MLA
Zhang, L., Wang, I., Solban, N., Cristescu, R., Zeng, G., Long, B."Comprehensive investigation of T and B cell receptor repertoires in an MC38 tumor model following murine anti‑PD‑1 administration". Molecular Medicine Reports 22.2 (2020): 975-985.
Chicago
Zhang, L., Wang, I., Solban, N., Cristescu, R., Zeng, G., Long, B."Comprehensive investigation of T and B cell receptor repertoires in an MC38 tumor model following murine anti‑PD‑1 administration". Molecular Medicine Reports 22, no. 2 (2020): 975-985. https://doi.org/10.3892/mmr.2020.11169