Abstract
Ran X, Xiao J, Zhang Y, et al. Low intratumor heterogeneity correlates with increased response to PD-1 blockade in renal cell carcinoma. Ther Adv Med Oncol 2020; 12: 1–17. DOI: 10.1177/1758835920977117
In the above-referenced article, the following information is updated:
Page 4, Figure 1, “MATH score separates low from high ITH in RCC”.
Association between MATH score and subclonal genome fraction determined by ABSOLUTE (1) in pRCC tumors (A), ccRCC tumors from TCGA (B) and Wang et al. (C). R and p-values are from Pearson’s correlation analyses. (D) The cutpoints of MATH scores based on the survival information (PFS and DSS, respectively) of the patients with pRCC from TCGA, and a MATH score of 31 achieved a stronger significance in distinguishing high from low subclonal genome fraction. (E) The cutpoints of MATH scores based on survival information (i.e. PFS) of the patients with ccRCC from TCGA (41) and those from the clinical trial of anti-PD-1 therapy (42), and a MATH score of 41 performed better in differentiating high from low subclonal genome fraction for ccRCC tumors from TCGA. (F) The MATH score that best distinguish high from low subclonal genome fraction in ccRCC tumors from Wang et al. ccRCC, clear cell renal cell carcinoma; DSS, disease-specific survival; ITH, intratumor heterogeneity; MATH, mutant-allele tumor heterogeneity; pRCC, papillary renal cell carcinoma; PFS, progression-free survival; RCC, renal cell carcinoma; TCGA, The Cancer Genome Atlas.”
Page 5, right column, paragraph 1, line 21, the correct sentence reads as “When a MATH score
of 54 was applied, not only DCs, but NK cells and B cells showed higher abundance in low-versus high-ITH tumors (DCs: p = 0.0006 by MCPCounter and p = 0.01 by quanTIseq; NK cells: p = 0.04 by MCPCounter and p = 0.011 by quanTIseq; B cells: p = 0.013 by MCPCounter and p = 0.006 by quanTIseq; Figure 2B).”
Page 5, right column, paragraph 2, line 9, the correct sentence reads as “In patients with ccRCC from TCGA, the combined neoantigen counts were significantly higher in lowversus high-ITH tumors (p = 0.036; Figure 2C), and similar trend was observed in neoAgs_InDels (p = 0.01; Figure S3A) but not neoAgs_SNVs (p = 0.34; Figure S3B).”
Page 5, right column, paragraph 2, line 15, the correct sentence reads as “In patients with ccRCC from Wang et al.,27 low-ITH tumors also show significantly higher combined neoantigen counts whether a MATH score of 41 (p = 1e-05; Figure 2C) or 54 (p = 0.003; Figure 2C) was used to differentiate high- from low-ITH tumors, yet similar trend was observed in neoAgs_SNVs (p = 5.7e-08 when the cutpoint of MATH score was 41 and p = 5e-05 when the cutpoint of MATH score was 54; Figure S3B) rather than neoAgs_ InDels (p = 0.076 when the cutpoint of MATH score was 41 and p = 0.381 when the cutpoint of MATH score was 54; Figure S3A).”
Page 7, left column, paragraph 2, line 8, the correct sentence reads as “Intriguingly, the RNA expression of all HLA class I genes was significantly lower in patients with high- versus low-ITH tumors from patients with ccRCC from TCGA (HLA-A: p = 0.001; HLA-B: p = 0.006; HLA-C: p = 0.001; HLA-E: p = 0.002;
HLA-F: p = 0.007; HLA-G: p = 0.024; B2M: p = 0.016; Figure 2D). Similar trends were also observed in ccRCC patients from Wang et al.,27 whether a MATH score of 41 (HLA-A: p = 0.015; HLA-B: p = 0.019; HLA-C: p = 0.020; HLA-E: p = 0.033; HLA-F: p = 0.022; HLA-G: p = 0.601; B2M: p = 0.035; Figure 2E) or 54 (HLA-A: p = 0.006; HLA-B: p = 0.024; HLA-C: p = 0.004; HLA-E: p = 0.002; HLA-F: p = 0.018; HLA-G: p = 0.269; B2M: p = 0.009; Figure 2F) was used to differentiate high- from low-ITH tumors, suggesting that immune escape might be more prevalent in high-ITH tumors from patients with ccRCC through HLA downregulation, an observation which had been described in lung squamous cell carcinoma.6”
Page 7, left column, paragraph 3, line 12, the correct reference for “Since PD-1 attenuates T-cell activation through interaction with PD-L1 and a second ligand – PD-L2” should read as “Wei SC, Duffy CR and Allison JP. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discovery 2018; 8(9): 1069-1086.”
In Figure 1A, B, and C, Pearson correlation coefficient should be “R” or “r” and not “R2”.
In Figure S3, A should be “Neoantigen counts derived from InDels”, B should be “Neoantigen counts derived from SNVs”. In addition, the correct p value for neoantigen counts from SNVs in ccRCC tumors from TCGA should be 0.01 not 0.34, while the correct p value for neoantigen counts from InDels in ccRCC tumors from TCGA should be 0.34 not 0.01. The correct Figure S3 has been updated.
The online version of the article has been corrected.