Prognostic Utility of Immunoprofiling in Colon Cancer: Results from a Prospective, Multicenter Nodal Ultrastaging Trial.
Retrospective data indicate that immunoprofiling of T cell markers can be prognostic in colon cancer. Prospective T cell immunoprofiling of colon cancer has not been well defined for patients whose lymph nodes are ultrastaged.



A prospective cohort was selected from patients enrolled in an ongoing phase II multicenter trial of nodal ultrastaging for colon cancer. Primary tumor specimens from 89 patients were analyzed by immunohistochemistry for the T cells CD3(+), CD4(+), CD8(+), and FOXP3(+). Lymphocyte populations were quantified with digital image analysis. Results were examined for their association with 5-year disease-free survival along with TNM stage and clinicopathologic variables.



Longer disease-free survival was associated with higher CD3(+) counts at the invasive margin (IM) (p = 0.005), higher CD8(+) counts at the tumor center (TC) and IM (p = 0.002), a lower CD4(+)/CD8(+) ratio at the TC+IM (p = 0.027), and a higher CD8(+)/FOXP3(+) ratio at the TC+IM (p = 0.020). After multivariable analysis, CD8(+) at the TC+IM (p = 0.002), the CD8(+)/FOXP3(+) ratio at the TC+IM (p = 0.004), and the number of tumor-positive lymph nodes (p = 0.003) remained significant.



This is the first prospective demonstration of the prognostic utility of immunoprofiling in colon cancer after nodal ultrastaging. Staging based on tumor immunoprofile can augment TNM staging and provide targets for specific immunotherapies.
Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
Devin C
DC
Flaherty
Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
Simon
S
Lavotshkin
Department of Pathology, Providence Saint John's Health Center, Santa Monica, CA.
John R
JR
Jalas
Melanoma Research Program and Department of Immunology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
Hitoe
H
Torisu-Itakura
Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
Daniel D
DD
Kirchoff
Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA.
Myung S
MS
Sim
Dirks/Dougherty Laboratory for Cancer Research and Department of Translational Immunology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA.
Delphine J
DJ
Lee
Department of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA; California Oncology Research Institute, Los Angeles, CA. Electronic address: bilchika@jwci.org.
Anton J
AJ
Bilchik
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003082:Colectomy; D003110:Colonic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism*
D014408:Biomarkers, Tumor; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors