CD8+ tumor‐infiltrating lymphocytes within the primary tumor of patients with synchronous de novo metastatic colorectal carcinoma do not track with survival
Objectives Tumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease stages (I‐II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to...
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Published in | Clinical & translational immunology Vol. 9; no. 7; pp. e1155 - n/a |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Australia
John Wiley & Sons, Inc
2020
John Wiley and Sons Inc Wiley |
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Abstract | Objectives
Tumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease stages (I‐II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC.
Methods
Treatment‐naïve patients (109) with mCRC were assessed for CD8+ TILs and PD‐L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel.
Results
Microsatellite instability‐high tumors had significantly more CD8+ TILs, with no significant survival advantage observed between MSI‐H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD‐L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI‐H tumors and associated immune cells had higher PD‐L1 expression than in MSS cases. A positive correlation between PD‐L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI‐H tumors.
Conclusion
In contrast to early‐stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD‐L1 comparable to MSI‐H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be.
Unlike early‐stage colorectal cancer (CRC), the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival despite MSI‐H tumors having higher tumor infiltrating lymphocytes (TILs). This unique cohort of patients with synchronous mCRC by definition represents the breakdown of immune containment of the primary tumor. Despite this, we also identified a subgroup of MSS tumors with a high TILs comparable to MSI‐H tumors and this group traditionally would not be considered for immune checkpoint blockade, and perhaps should be. |
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AbstractList | ObjectivesTumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease stages (I‐II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC.MethodsTreatment‐naïve patients (109) with mCRC were assessed for CD8+ TILs and PD‐L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel.ResultsMicrosatellite instability‐high tumors had significantly more CD8+ TILs, with no significant survival advantage observed between MSI‐H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD‐L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI‐H tumors and associated immune cells had higher PD‐L1 expression than in MSS cases. A positive correlation between PD‐L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI‐H tumors.ConclusionIn contrast to early‐stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD‐L1 comparable to MSI‐H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be. Tumor-infiltrating lymphocytes (TIL), particularly CD8 TILs in patients with colorectal cancer (CRC), are highly prognostic in the early-disease stages (I-II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented with mCRC. Treatment-naïve patients (109) with mCRC were assessed for CD8 TILs and PD-L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel. Microsatellite instability-high tumors had significantly more CD8 TILs, with no significant survival advantage observed between MSI-H and microsatellite stable (MSS) tumors (12 vs 19 months, = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, = 0.426), while PD-L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; = 0.038). MSI-H tumors and associated immune cells had higher PD-L1 expression than in MSS cases. A positive correlation between PD-L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI-H tumors. In contrast to early-stage CRC, the immune response in primary tumors of patients with mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD-L1 comparable to MSI-H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be. Objectives Tumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease stages (I‐II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC. Methods Treatment‐naïve patients (109) with mCRC were assessed for CD8+ TILs and PD‐L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel. Results Microsatellite instability‐high tumors had significantly more CD8+ TILs, with no significant survival advantage observed between MSI‐H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD‐L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI‐H tumors and associated immune cells had higher PD‐L1 expression than in MSS cases. A positive correlation between PD‐L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI‐H tumors. Conclusion In contrast to early‐stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD‐L1 comparable to MSI‐H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be. Unlike early‐stage colorectal cancer (CRC), the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival despite MSI‐H tumors having higher tumor infiltrating lymphocytes (TILs). This unique cohort of patients with synchronous mCRC by definition represents the breakdown of immune containment of the primary tumor. Despite this, we also identified a subgroup of MSS tumors with a high TILs comparable to MSI‐H tumors and this group traditionally would not be considered for immune checkpoint blockade, and perhaps should be. Abstract Objectives Tumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease stages (I‐II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC. Methods Treatment‐naïve patients (109) with mCRC were assessed for CD8+ TILs and PD‐L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel. Results Microsatellite instability‐high tumors had significantly more CD8+ TILs, with no significant survival advantage observed between MSI‐H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD‐L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI‐H tumors and associated immune cells had higher PD‐L1 expression than in MSS cases. A positive correlation between PD‐L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI‐H tumors. Conclusion In contrast to early‐stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD‐L1 comparable to MSI‐H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be. Unlike early‐stage colorectal cancer (CRC), the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival despite MSI‐H tumors having higher tumor infiltrating lymphocytes (TILs). This unique cohort of patients with synchronous mCRC by definition represents the breakdown of immune containment of the primary tumor. Despite this, we also identified a subgroup of MSS tumors with a high TILs comparable to MSI‐H tumors and this group traditionally would not be considered for immune checkpoint blockade, and perhaps should be. Abstract Objectives Tumor‐infiltrating lymphocytes (TIL), particularly CD8 + TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease stages (I‐II). In metastatic disease (stage IV; mCRC), their influence is less well defined. It has presumably failed to contain tumor cells to the primary site; however, is this evident? We explored the prognostic impact of TILs at the primary site in patients who presented de novo with mCRC. Methods Treatment‐naïve patients (109) with mCRC were assessed for CD8 + TILs and PD‐L1 expression. Microsatellite instability (MSI) was evaluated by IHC for PMS2 and MSH6 proteins and/or by PCR using the Bethesda panel. Results Microsatellite instability‐high tumors had significantly more CD8 + TILs, with no significant survival advantage observed between MSI‐H and microsatellite stable (MSS) tumors (12 vs 19 months, P = 0.304). TIL density for all cases had no impact on OS (low: 20 vs high: 13 months, P = 0.426), while PD‐L1 of 1% or higher was associated with reduced mean survival (9.6 vs 18.9 months; P = 0.038). MSI‐H tumors and associated immune cells had higher PD‐L1 expression than in MSS cases. A positive correlation between PD‐L1 on immune cells and CD8+ve TILs was found. A subset of MSS tumors had relatively high TILs approximating that of MSI‐H tumors. Conclusion In contrast to early‐stage CRC, the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival. A subgroup of MSS tumors was identified with increased TILs/PD‐L1 comparable to MSI‐H tumors, traditionally not be considered for immune checkpoint blockade and perhaps should be. |
Author | Hendry, Shona Abbott, Rebecca Wong, Hui‐Li Visvanathan, Kumar Gibbs, Peter Tie, Jeanne Tran, Ben Kosmider, Suzanne Fox, Stephen Desai, Jayesh Millen, Rosemary Croxford, Matthew Zalcberg, John Narasimhan, Vignesh Ramsay, Robert G Jones, Ian Byrne, David |
AuthorAffiliation | 2 Sir Peter MacCallum Department of Oncology University of Melbourne Melbourne VIC Australia 11 University of Melbourne Melbourne VIC Australia 1 Peter MacCallum Cancer Centre Melbourne VIC Australia 7 Royal Melbourne Hospital Melbourne VIC Australia 9 Monash University Melbourne VIC Australia 4 Department of Anatomical Pathology St Vincent's Hospital Melbourne Melbourne VIC Australia 5 Department of Pathology University of Melbourne Melbourne VIC Australia 8 Walter and Eliza Hall Institute Parkville VIC Australia 3 St. Vincent's Hospital Melbourne VIC Australia 6 Western Health Footscray VIC Australia 10 Alfred Health Prahran VIC Australia |
AuthorAffiliation_xml | – name: 2 Sir Peter MacCallum Department of Oncology University of Melbourne Melbourne VIC Australia – name: 8 Walter and Eliza Hall Institute Parkville VIC Australia – name: 6 Western Health Footscray VIC Australia – name: 10 Alfred Health Prahran VIC Australia – name: 9 Monash University Melbourne VIC Australia – name: 1 Peter MacCallum Cancer Centre Melbourne VIC Australia – name: 7 Royal Melbourne Hospital Melbourne VIC Australia – name: 5 Department of Pathology University of Melbourne Melbourne VIC Australia – name: 3 St. Vincent's Hospital Melbourne VIC Australia – name: 11 University of Melbourne Melbourne VIC Australia – name: 4 Department of Anatomical Pathology St Vincent's Hospital Melbourne Melbourne VIC Australia |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32953115$$D View this record in MEDLINE/PubMed |
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Copyright | 2020 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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Keywords | tumor infiltrating lymphocytes advanced metastatic colorectal cancer PD‐L1 |
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Tumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease... Tumor-infiltrating lymphocytes (TIL), particularly CD8 TILs in patients with colorectal cancer (CRC), are highly prognostic in the early-disease stages (I-II).... Abstract Objectives Tumor‐infiltrating lymphocytes (TIL), particularly CD8 + TILs in patients with colorectal cancer (CRC), are highly prognostic in the... ObjectivesTumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the early‐disease... Unlike early‐stage colorectal cancer (CRC), the immune response in primary tumors of patients with de novo mCRC does not appear to influence survival despite... Abstract Objectives Tumor‐infiltrating lymphocytes (TIL), particularly CD8+ TILs in patients with colorectal cancer (CRC), are highly prognostic in the... |
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SubjectTerms | advanced metastatic colorectal cancer Antibodies Biomarkers CD8 antigen Colorectal cancer Colorectal carcinoma Cytotoxicity Immune checkpoint Immune response Lymphocytes Medical prognosis Metastases Metastasis Microsatellite instability MSH6 protein Original Patients PD-L1 protein PD‐L1 Studies Tumor cells tumor infiltrating lymphocytes Tumors |
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Title | CD8+ tumor‐infiltrating lymphocytes within the primary tumor of patients with synchronous de novo metastatic colorectal carcinoma do not track with survival |
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