Dataset Information

CD169⁺ sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.

ABSTRACT:

Aims

Mismatch-repair deficiency and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) is treated with programmed death (PD)-1 antibody regardless of PD-ligand (L)1 expression in tumor cells. We previously found that abundant CD169⁺ macrophages in regional lymph node (RLN) sinuses and CD8⁺ tumor-infiltrating lymphocytes (TILs) positively correlated in CRC and were associated with a favorable prognosis. However, associations between dMMR/MSI-H CRC and CD8⁺ TILs or prognoses vary among studies. In this study, we attempted to compare the association between MMR status, CD169⁺ macrophages in RLNs, CD8⁺ TILs, PD-L1 scores, and prognoses in CRC.

Methods and results

We immunostained 83 surgically resected CRC tumors that we previously analyzed for MMR proteins, and identified 9 that were dMMR. The number of CD169⁺ macrophages in RLNs and CD8⁺ TILs significantly correlated with overall survival, whereas MMR status did not. The number of cells positive for the TIL markers CD3, CD4, CD8, and TIA-1, and macrophage markers CD68 and CD169 in RLNs did not significantly differ between groups according to MMR status. Furthermore, combined positive scores (CPS) for PD-L1 expression in five of nine dMMR CRCs were all <1. We found that dMMR in CRC did not correlate with numbers of CD169⁺ macrophages in RLNs or CD8⁺ TILs.

Conclusions

CRC with CD169⁺ macrophages in RLNs and abundant CD8⁺ TILs indicates a better prognosis and it should be immunologically classified as a different antitumor group from dMMR CRC.

SUBMITTER: Saito Y

PROVIDER: S-EPMC10225197 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

CD169<sup>+</sup> sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.

Saito Yoichi Y Fujiwara Yukio Y Miyamoto Yuji Y Ohnishi Koji K Nakashima Yuta Y Tabata Yasuhiko Y Baba Hideo H Komohara Yoshihiro Y

Cancer medicine 20230227 9

<h4>Aims</h4>Mismatch-repair deficiency and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) is treated with programmed death (PD)-1 antibody regardless of PD-ligand (L)1 expression in tumor cells. We previously found that abundant CD169<sup>+</sup> macrophages in regional lymph node (RLN) sinuses and CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) positively correlated in CRC and were associated with a favorable prognosis. However, associations between dMMR/MSI-H CRC a ...[more]

PMID: 36846928

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Project description:BackgroundPropionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions.MethodsWe evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of P. acnes.ResultsSmall round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming P. acnes). MT treatment revealed abundant IIC-forming P. acnes in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming P. acnes was detected in control samples without inflammation. IIC-forming P. acnes were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming P. acnes. Conventional electron microscopy identified many SRBs (0.5-2.0 μm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming P. acnes, some of which were in phagolysosomes with a degraded and lamellar appearance.ConclusionsP. acnes-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.

Dataset Information

CD169⁺ sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.

Aims

Methods and results

Conclusions

Publications

CD169<sup>+</sup> sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

CD169+ sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.

Aims

Methods and results

Conclusions

Publications

CD169<sup>+</sup> sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CD169⁺ sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer.