1/27/2024 0 Comments Hopital jean mermoz 69008Only patients with a high immune response will be eligible for the POCHI trial. Tumours will then be classified as having a "high" or "low" immune response according to type of lymphocyte infiltrate, which is independent of pre-analytic conditions. Slides will be scanned and analysed by image analysis as previously described. For each patient, slides containing tumour tissue and adjacent non-tumour tissue will be analysed using two techniques : immunoscore® and TuLIS score.It consist in Immunohistochemistry with CD3 and CD8 staining. Therefore, blocks of resected primary tumour will be collected and analysed prospectively. Investigators formulated the hypothesis that patients with a pMMR CRC with a high immune infiltrate can be sensitive to ICI. Finally, approximately 14% of tumours with a high immune infiltrate have been found in patients with metastatic CRC. has also a high prognostic value in CRC and is based on CD3+ and CD8+ T cells infiltration in the center and periphery of the tumour. An immunoscore® described by Galon et al. Patients presenting with a pMMR CRC with a high immune infiltrate had a better progression-free survival (HR=0.70 p=0.02). Automated tests evaluating TIL are performed on virtual slides and have showed that, out of 1,220 tumours tested, 20% were highly infiltrated by CD3+ T cells. Previously, investigators described an automated and reproducible method for analysis of TIL and investigators validated it for clinical use. However, no validated test is used in routine clinical practice. The prognostic value of lymphocyte infiltrate has been demonstrated in CRC by several teams. Lastly, immunogenic cell death induced by chemotherapy, such as oxaliplatin, can increase the efficacy of ICI. However, it is possible that 20% of pMMR mCRC with a high CD3+ infiltrate in the tumour may be a subgroup of pMMR mCRC sensitive to ICI, as is the case for dMMR mCRC. pMMR mCRC did not seem to benefit from anti-PD1 antibodies. Anti-PD1 antibodies have recently been reported as being very effective in patients with dMMR metastatic CRC (mCRC). Pembrolizumab, an anti-PD1 monoclonal antibody (programmed death-1) is an immune checkpoint inhibitor (ICI) of PD1/PD-L1 axis, recently approved in many cancers. This same immune score has made it possible to measure high lymphocyte infiltration in hepatic metastases, in particular, in patients treated with XELOX/FOLFOX. Investigators recently showed, with a prospectively validated immune score, that 14% of localised MSS/pMMR CRC are also highly infiltrated by CD3+ lymphocytes. These latter are characterised by generation of many neo-antigens, which result in a high anti-tumour immune response and a high peri- and/or intra-tumour lymphocyte infiltration (TIL). 15%, are "microsatellite unstable" (MSI) with deficient DNA Mismatch-Repair system (dMMR). About 85% of cases of non-metastatic colorectal cancer (CRC) are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR) which are also called CRC with microsatellite stability (MSS).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |