Abstract
In colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3+ T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p =.0018) and disease-specific survival (DSS) (not reached vs. 48 months, p =.0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes.
| Original language | English |
|---|---|
| Article number | 2253642 |
| Number of pages | 7 |
| Journal | Oncoimmunology |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2023 |
Bibliographical note
Funding Information:Outside the submitted work, S.T. has received consultant fees from Bristol Myers Squibb and Turnstone Biologics, speaking fees from Celgene and Astra Zeneca, and has research funding from Iovance Biotherapeutics and Turnstone Biologics.
Funding Information:
This study was supported by the Université de Montréal Roger Des Groseillers Research Chair in Hepatopancreatobiliary Surgical Oncology. ST and AMMM are Researchers of the Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM)/which receive support from the Fonds de recherche du Québec - Santé (FRQS). ST was supported by the Fonds de recherche du Québec–Santé (FRQ-S) Young Clinician Scientist Seed Grant No. 32633; FRQS Clinician Scientist Junior-1 Salary Award No. 30861; and Institut du Cancer de Montréal establishment award. DH was supported by the FRQ-S phase 1 award for medical residents engaged in clinician-scientist training; NM was supported by the International Hepato-Pancreato-Biliary Association (IHPBA) Kenneth Warren Research Fellowship and Ethicon Inc. (Johnson & Johnson). We thank the patients for providing access to their tissues and data for research; L. Rousseau, J. Bilodeau, and S. Langevin from the CHUM hepatopancreatobiliary cancer biobank for patient recruitment, prospective data, and biospecimen acquisition; L. Meunier and V. Barrès from the CRCHUM histology platform for building the tissue microarray and high-resolution scanning; and A. Cleret-Bohot from the CRCHUM microscopy platform for assistance with automated quantification.
Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
Keywords
- Colorectal liver metastasis
- immune score
- prognostic biomarker
- tumor heterogeneity
- tumor infiltrating lymphocytes