TY - JOUR
T1 - Tumor Immunogenomic Features Determine Outcomes in Patients with Metastatic Colorectal Cancer Treated with Standard-of-Care Combinations of Bevacizumab and Cetuximab
AU - Innocenti, Federico
AU - Yazdani, Akram
AU - Rashid, Naim
AU - Qu, Xueping
AU - Ou, Fang Shu
AU - Van Buren, Scott
AU - Bertagnolli, Monica M.
AU - Kabbarah, Omar
AU - Blanke, Charles David
AU - Venook, Alan P.
AU - Lenz, Heinz Josef
AU - Vincent, Benjamin G.
N1 - Publisher Copyright:
© 2022 American Association for Cancer Research.
PY - 2022/4/15
Y1 - 2022/4/15
N2 - Purpose: CALGB/SWOG 80405 was a randomized phase III trial in first-line patients with metastatic colorectal cancer treated with bevacizumab, cetuximab, or both, plus chemotherapy.We tested the effect of tumor immune features on overall survival (OS). Experimental Design: Primary tumors (N = 554) were profiled by RNA sequencing. Immune signatures of macrophages, lymphocytes, TGFb, IFNg, wound healing, and cytotoxicity were measured. CIBERSORTx scores of naive and memory B cells, plasma cells, CD8+ T cells, resting and activated memory CD4+ T cells, M0 and M2 macrophages, and activated mast cells were measured. Results: Increased M2 macrophage score [HR, 6.30; 95% confidence interval (CI), 3.0-12.15] and TGFb signature expression (HR, 1.35; 95% CI, 1.05-1.77) were associated with shorter OS. Increased scores of plasma cells (HR, 0.55; 95% CI, 0.38-0.87) and activated memory CD4+ T cells (HR, 0.34; 95% CI, 0.16-0.65) were associated with longer OS. Using optimal cutoffs from these four features, patients were categorized as having either 4, 3, 2, or 0-1 beneficial features associated with longer OS, and the median (95% CI) OS decreased from 42.5 (35.8-47.8) to 31.0 (28.8- 34.4), 25.2 (20.6-27.9), and 17.7 (13.5-20.4) months respectively (P = 3.48e-11). Conclusions: New immune features can be further evaluated to improve patient response. They provide the rationale for more effective immunotherapy strategies.
AB - Purpose: CALGB/SWOG 80405 was a randomized phase III trial in first-line patients with metastatic colorectal cancer treated with bevacizumab, cetuximab, or both, plus chemotherapy.We tested the effect of tumor immune features on overall survival (OS). Experimental Design: Primary tumors (N = 554) were profiled by RNA sequencing. Immune signatures of macrophages, lymphocytes, TGFb, IFNg, wound healing, and cytotoxicity were measured. CIBERSORTx scores of naive and memory B cells, plasma cells, CD8+ T cells, resting and activated memory CD4+ T cells, M0 and M2 macrophages, and activated mast cells were measured. Results: Increased M2 macrophage score [HR, 6.30; 95% confidence interval (CI), 3.0-12.15] and TGFb signature expression (HR, 1.35; 95% CI, 1.05-1.77) were associated with shorter OS. Increased scores of plasma cells (HR, 0.55; 95% CI, 0.38-0.87) and activated memory CD4+ T cells (HR, 0.34; 95% CI, 0.16-0.65) were associated with longer OS. Using optimal cutoffs from these four features, patients were categorized as having either 4, 3, 2, or 0-1 beneficial features associated with longer OS, and the median (95% CI) OS decreased from 42.5 (35.8-47.8) to 31.0 (28.8- 34.4), 25.2 (20.6-27.9), and 17.7 (13.5-20.4) months respectively (P = 3.48e-11). Conclusions: New immune features can be further evaluated to improve patient response. They provide the rationale for more effective immunotherapy strategies.
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U2 - 10.1158/1078-0432.CCR-21-3202
DO - 10.1158/1078-0432.CCR-21-3202
M3 - Article
C2 - 35176136
AN - SCOPUS:85128459094
SN - 1078-0432
VL - 28
SP - 1690
EP - 1700
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -