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752 The impact of grade of differentiation and BRAF mutation status on neoantigen and immune landscape in papillary thyroid cancer
  1. Myungwoo Nam1,
  2. Myungwoo Nam1,
  3. Woojung Yang1,
  4. Ju Young Lee1,
  5. Jaeyoun Choi1,
  6. Hansol Choi1,
  7. Emma Yu1,
  8. Eugene Kim1,
  9. Jin Young Hwang1,
  10. William Bae1,
  11. Chan Mi Jung1,
  12. Victor Wang2,
  13. Jeffrey Chuang2 and
  14. Young Kwang Chae1
  1. 1Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  2. 2The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA


Background The use of immune checkpoint inhibitors (ICIs) in cancer treatment has been approved by the FDA, but its application is experimental in the treatment of papillary thyroid cancer (PTC). Induction of immune response via recognition of neoantigens is considered to be the basis for the treatment mechanism of ICIs.1 However, the neoantigen landscape has not been explored in PTC. Our aim is to investigate the immune landscape of PTC in relation to neoantigens, taking into account the BRAF mutation status and grade of differentiation as contributing factors.

Methods BRAF V600E mutation status and thyroid differentiation scores (TDSs) were gathered from the PTC cohort of The Cancer Genome Atlas (TCGA). TDS was derived from the mRNA expression levels of 16 thyroid function genes to quantify the grade of differentiation. Tumors with TDSs in the 1st quartile and 4th quartile were defined as poorly differentiated and well differentiated, respectively. The neoantigen burden for each sample was predicted using CloudNeo pipeline. The infiltration of immune cells was calculated through CIBERSORT.

Results Among 400 patients with predicted neoantigen data, 187 (47%) had BRAF mutations. The BRAF mutated tumors showed increased cytolytic activity score (CYT, p=0.001), increased infiltration of regulatory T cells (Treg, p<0.001), and higher PD-L1 expression (p<0.001) compared to BRAF wild-type tumors (figure 1). In regard to grade of differentiation, poorly differentiated tumors showed increased CYT (p=0.002), increased infiltration of Treg (p<0.001), and higher PD-L1 expression (p<0.001) compared to well differentiated tumors (figure 2). However, BRAF mutation status or grade of differentiation did not correlate with the neoantigen burden. Also, the neoantigen burden did not show any correlations with immune landscape features such as infiltration of CD8+ T cells or Treg, CYT, and PD-L1 expression.

Abstract 752 Figure 1

Immune traits according to BRAF mutation status. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.

Abstract 752 Figure 2

Immune traits according to grade of differentiation. (a) Cytolytic activity score(CYT). (b) Infiltration of regulatory T cells(Tregs). (c) PD-L1 expression.

Conclusions Increased CYT and higher expression of PD-L1 in the BRAF mutated or the poorly differentiated tumors imply the possible role of ICI use in these subgroups of patients. However, the immune response to these subgroups does not seem to be mediated through the increase in neoantigen formation. Further studies are warranted to explore markers for immunotherapy implication.


  1. Schumacher TN, Schreiber RD, Neoantigens in cancer immunotherapy. Science 2015; 348:69–74.

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