Multimodal Immune Profile Score (IPS) as a Pan-Cancer Biomarker for Stratifying Outcomes of Immune Checkpoint Inhibitor Benefit in Microsatellite Stable Colorectal Cancer and Rare Solid Tumors
- 1Tempus AI, Inc., Chicago, IL
Abstract
Background Immune checkpoint inhibitor (ICI) therapies have revolutionized oncology, but identifying patients who benefit remains a challenge, particularly in populations where ICIs are not the standard of care, including microsatellite stable colorectal cancer (MSS CRC) and rare solid cancers. We evaluated real-world performance of the Immune Profile Score (IPS), a validated DNA- and RNA-based molecular signature, in these cohorts. Methods In an exploratory analysis, we analyzed two real-world cohorts: 1) MSS CRC; and 2) MSS, tumor mutational burden-low rare solid cancers treated with off-label ICI. IPS-High and IPS-Low were calculated using a previously validated threshold. Cox proportional hazards models were fit to demonstrate prognostic utility for real-world overall survival (rwOS). In MSS CRC, time-to-next-treatment (TTNT) on prior non-ICI therapy was compared to rwOS on subsequent ICI therapy. Results In MSS CRC (n=46), IPS-High patients (13%) demonstrated clinically meaningful improvement in rwOS versus IPS-Low (Median OS: not reached vs 7.3 months; HR = 0.22, 90% CI 0.04-1.16). While IPS was not associated with TTNT on the preceding non-ICI line (HR = 1.07, 90% CI 0.60-1.91), it was associated with OS in patients receiving later line ICI (HR 0.21, 90% CI 0.04-1.22). In the rare cancers cohort (n=90; 26 unique malignancies), IPS-High (17.8%) was associated with longer OS to ICI therapy (HR = 0.26, 90% CI 0.11-0.61), even when restricted to histologies represented in both IPS groups (HR = 0.18, 90%, CI 0.05-0.62). Conclusions Preliminary evidence suggests that IPS may serve as a generalizable, pan-cancer biomarker capable of stratifying outcomes for ICI treatment in populations traditionally excluded from immunotherapy benefit.
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BibTeX
@misc{tinglin2026multimodal,
title = {{Multimodal Immune Profile Score (IPS) as a Pan-Cancer Biomarker for Stratifying Outcomes of Immune Checkpoint Inhibitor Benefit in Microsatellite Stable Colorectal Cancer and Rare Solid Tumors}},
author = {M. A. Ting-Lin and E. S. Antonarakis and X. Wang and R. Erbe and A. D. Zander and Y. Liu and A. Jin and G. A. Vidal and S. M. Haake and M. M. Stein and D. F. DeSantis and K. A. Beauchamp and M. E. Campbell and E. E. W. Cohen and S. W. Hyun and R. J. Kelly and A. Kalyan and B. Bashir and B. J. Rimel and T. J. Herzog and V. L. Chiou and C. Sangli and H. Nimeiri and J. Carlson and D. M. Simeone and J. H. Strickler},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.26364989},
url = {https://www.medrxiv.org/content/10.64898/2026.10.07.26364989v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Multimodal Immune Profile Score (IPS) as a Pan-Cancer Biomarker for Stratifying Outcomes of Immune Checkpoint Inhibitor Benefit in Microsatellite Stable Colorectal Cancer and Rare Solid Tumors
AU - M. A. Ting-Lin
AU - E. S. Antonarakis
AU - X. Wang
AU - R. Erbe
AU - A. D. Zander
AU - Y. Liu
AU - A. Jin
AU - G. A. Vidal
AU - S. M. Haake
AU - M. M. Stein
AU - D. F. DeSantis
AU - K. A. Beauchamp
AU - M. E. Campbell
AU - E. E. W. Cohen
AU - S. W. Hyun
AU - R. J. Kelly
AU - A. Kalyan
AU - B. Bashir
AU - B. J. Rimel
AU - T. J. Herzog
AU - V. L. Chiou
AU - C. Sangli
AU - H. Nimeiri
AU - J. Carlson
AU - D. M. Simeone
AU - J. H. Strickler
PY - 2026
DA - 2026/10/07
PB - medRxiv
DO - 10.64898/2026.10.07.26364989
UR - https://www.medrxiv.org/content/10.64898/2026.10.07.26364989v1
AB - Background Immune checkpoint inhibitor (ICI) therapies have revolutionized oncology, but identifying patients who benefit remains a challenge, particularly in populations where ICIs are not the standard of care, including microsatellite stable colorectal cancer (MSS CRC) and rare solid cancers. We evaluated real-world performance of the Immune Profile Score (IPS), a validated DNA- and RNA-based molecular signature, in these cohorts. Methods In an exploratory analysis, we analyzed two real-world cohorts: 1) MSS CRC; and 2) MSS, tumor mutational burden-low rare solid cancers treated with off-label ICI. IPS-High and IPS-Low were calculated using a previously validated threshold. Cox proportional hazards models were fit to demonstrate prognostic utility for real-world overall survival (rwOS). In MSS CRC, time-to-next-treatment (TTNT) on prior non-ICI therapy was compared to rwOS on subsequent ICI therapy. Results In MSS CRC (n=46), IPS-High patients (13%) demonstrated clinically meaningful improvement in rwOS versus IPS-Low (Median OS: not reached vs 7.3 months; HR = 0.22, 90% CI 0.04-1.16). While IPS was not associated with TTNT on the preceding non-ICI line (HR = 1.07, 90% CI 0.60-1.91), it was associated with OS in patients receiving later line ICI (HR 0.21, 90% CI 0.04-1.22). In the rare cancers cohort (n=90; 26 unique malignancies), IPS-High (17.8%) was associated with longer OS to ICI therapy (HR = 0.26, 90% CI 0.11-0.61), even when restricted to histologies represented in both IPS groups (HR = 0.18, 90%, CI 0.05-0.62). Conclusions Preliminary evidence suggests that IPS may serve as a generalizable, pan-cancer biomarker capable of stratifying outcomes for ICI treatment in populations traditionally excluded from immunotherapy benefit.
ER -