Supplementary Materials

Supplementary Material for:

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

Whijae Roh, Pei-Ling Chen, Alexandre Reuben, Christine N. Spencer, Peter A. Prieto, John P. Miller, Vancheswaran Gopalakrishnan, Feng Wang, Zachary A. Cooper, Sangeetha M. Reddy, Curtis Gumbs, Latasha Little, Qing Chang, Wei-Shen Chen, Khalida Wani, Mariana Petaccia De Macedo, Eveline Chen, Jacob L. Austin-Breneman, Hong Jiang, Jason Roszik, Michael T. Tetzlaff, Michael A. Davies, Jeffrey E. Gershenwald, Hussein Tawbi, Alexander J. Lazar, Patrick Hwu, Wen-Jen Hwu, Adi Diab, Isabella C. Glitza, Sapna P. Patel, Scott E. Woodman, Rodabe N. Amaria, Victor G. Prieto, Jianhua Hu, Padmanee Sharma, James P. Allison, Lynda Chin, Jianhua Zhang, Jennifer A. Wargo,* P. Andrew Futreal*

*Corresponding author. Email: afutreal{at}mdanderson.org (P.A.F.); jwargo{at}mdanderson.org (J.A.W.)

Published 1 March 2017, Sci. Transl. Med. 9, eaah3560 (2017)
DOI: 10.1126/scitranslmed.aah3560

This PDF file includes:

  • Fig. S1. Workflow diagram of multidimensional profiling analysis.
  • Fig. S2. Distribution of sequencing coverage and tumor purities across samples.
  • Fig. S3. Mutational load, neoantigen load, and clinical response.
  • Fig. S4. ITH and clinical response.
  • Fig. S5. The effects of previous CTLA-4 blockade exposure on the baseline TCR clonality of pre–PD-1 blockade samples.
  • Fig. S6. Burden of CNAs in responders versus nonresponders.
  • Fig. S7. Copy number profiles of responders and DNRs.
  • Fig. S8. Correlation between burden of copy number loss and mutational load.
  • Fig. S9. Correlation between burden of copy number loss and mutational load in the Van Allen cohort.
  • Fig. S10. SGOL scores in three patient subgroups from the Van Allen cohort.
  • Fig. S11. Burden of recurrent CNAs in patients from the Van Allen cohort.
  • Fig. S12. Correlation between burden of copy number loss and immune scores.
  • Fig. S13. Up- and down-regulated pathways in patients with high copy number loss versus low copy number loss in the Van Allen cohort.
  • Fig. S14. Patient stratification based on mutational load and burden of copy number loss in the Van Allen cohort.
  • Legends for tables S1 to S18

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Other Supplementary Material for this manuscript includes the following:

  • Table S1 (Microsoft Excel format). Clinical and demographic characteristics of patient cohort.
  • Table S2 (Microsoft Excel format). Sample information, tumor purity, mutational load, neoantigen load, number of clones per tumor, and burden of CNAs.
  • Table S3 (Microsoft Excel format). Summary measure of the data across clinical subgroups.
  • Table S4 (Microsoft Excel format). List of somatic point mutations and indels.
  • Table S5 (Microsoft Excel format). List of HLA somatic mutations.
  • Table S6 (Microsoft Excel format). List of neoantigens and predicted major histocompatibility complex binding affinity.
  • Table S7 (Microsoft Excel format). TCR clonality.
  • Table S8 (Microsoft Excel format). Log2-transformed NanoString normalized count data in our cohort.
  • Table S9 (Microsoft Excel format). Immune scores (NanoString) in our cohort.
  • Table S10 (Microsoft Excel format). Log2 copy number ratio segment file by Sequenza in our cohort.
  • Table S11 (Microsoft Excel format). Recurrent CNAs in DNRs with copy number loss burden higher than 2000.
  • Table S12 (Microsoft Excel format). Log2 copy number ratio segment file by Sequenza in the Van Allen cohort.
  • Table S13 (Microsoft Excel format). Burden of CNAs in the Van Allen cohort.
  • Table S14 (Microsoft Excel format). Recurrent CNAs in the Van Allen cohort.
  • Table S15 (Microsoft Excel format). Relative contribution of copy number loss burden on chromosome 10 in CTLA-4 blockade resistance.
  • Table S16 (Microsoft Excel format). Immune scores (RNA-seq) in the Van Allen cohort.
  • Table S17 (Microsoft Excel format). Preranked gene list for GSEA, KEGG pathway, and GO analysis in the Van Allen cohort.
  • Table S18 (Microsoft Excel format). Additive effects of high mutational load and low burden of copy number loss on response to CTLA-4 blockade.

[Download Tables S1 to S18]