Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC)



Recent studies have shown an association in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45, and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS).


The study cohort included patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined.


Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS.


This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.

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American Joint Committee on Cancer


body mass index


colorectal cancer


cytoreductive surgery


disease-free survival


formalin-fixed paraffin-embedded


heated intraperitoneal chemotherapy


invasive margin


institutional review board


modified folinic acid, fluorouracil, and oxaliplatin treatment


microsatellite instability


microsatellite stability


overall survival


Peritoneal Cancer Index


residual tumor status


cure/complete remission


microscopic residual tumor


macroscopic residual tumor


tumor center


tumor-infiltrating lymphocytes


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This study was supported, in part, by the Smith Family Fund and the Comprehensive Cancer Center of Wake Forest University, and the tumor tissue pathology shared resource supported by NCI CCSG P30CA012197.

Author information




Garland-Kledzik: project development, data analysis, data collection, manuscript writing/editing; Uppal: project development, manuscript writing/editing; Naeini: data analysis; Stern: data analysis; Erali: project development; Yi: data collection; Cummins-Perry: data collection; Scholer: data analysis; Khader: data analysis; Santamaria-Barria: data analysis; Votanopoulos: data collection; Shen: data collection; Levine: project design, data collection; Bilchik: project development, manuscript writing/editing.

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Correspondence to Anton J. Bilchik MD.

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Garland-Kledzik, M., Uppal, A., Naeini, Y.B. et al. Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC). J Gastrointest Surg (2020).

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  • Peritoneal carcinomatosis
  • Immune profiling