Abstract Introduction: We aimed to assess the role of local adaptive immunity in the metastatic process by comparing densities of adaptive immune cells between normal colorectal mucosa (NM), primary colorectal cancer (pCRC) and liver metastases (LM) in patients with synchronous and metachronous disease. Patients and Methods: We enrolled patients, who underwent resection of pCRC and LM in Pilsen University Hospital between 1999 and 2022. 56 patients presented with LM (stage IV, synchronous) and 43 patients (stage II/III) developed LM later (metachronous). After immunohistochemical staining and whole slide scanning densities of CD3+ and CD8+ T cells and CD20+ B cells were quantified in NM, pCRC and LM using QuPath software. In pCRC and LM cell densities were measured in tumor center (TC), inner margin (IM), outer margin (OM) and peritumor (PT) region. IM and OM were defined as 500 µm on each side of the invasive tumor border. Results: For all examined cells in both groups we found smaller densities in TC of pCRC and LM compared to NM (Table). In pCRC of synchronous group compared to LM densities of all cells were smaller in IM and OM and densities of CD3+ and CD8+ cells were smaller in PT region. In pCRC of metachronous group compared to LM densities of all cells were greater in TC, densities of CD3+ were smaller in OM and PT region, whereas densities of CD20+ cells were smaller only in OM. Compared to metachronous group patients with synchronous metastases had smaller densities of CD3+ T cells in IM and CD8+ T cells in TC and IM of pCRC. Conclusion: Development of pCRC is accompanied by decreased densities of T and B cells in TC compared to NM, which further decrease in metachronous LM. Lower densities of T and B cells in IM and OM and T cells in PT region of pCRC compared to LM is a hallmark of synchronous group. TC of pCRC harbors larger numbers of T and B cells compared to LM in metachronous group. Low numbers of CD3+ and CD8+ T cells in IM and CD8+ T cells in TC of primary CRC may contribute to development of synchronous metastases. Densities of CD3+, CD8+ and CD20+ cells per mm2 of the tissue (median) Patients witn liver metastases Synchronous Metachronous NM pCRC LM NM pCRC LM CD3 NM 1014 1042 CD3 TC 313p<0.05 to NM 249p<0.05 to NM 338p<0.05 to NM 199p<0.05 to NM and pCRC CD3 IM 252 431p<0.05 to pCRC 393p<0.05 to pCRC in synchronous group 483 CD3 OM 521 1437p<0.05 to pCRC 649 1953p<0.05 to pCRC CD3 PT 479 873p<0.05 to pCRC 447 987p<0.05 to pCRC CD8 NM 319 390 CD8 TC 58p<0.05 to NM 52p<0.05 to NM 102p<0.05 to NM and to pCRC in synchronous group 52p<0.05 to NM and pCRC CD8 IM 65 96p<0.05 to pCRC 102p<0.05 to pCRC in synchronous group 120 CD8 OM 206 559p<0.05 to pCRC 310 363 CD8 PT 177 369p<0.05 to pCRC 218 291 CD20 NM 331 215 CD20 TC 32p<0.05 to NM 11p<0.05 to NM 27p<0.05 to NM 12p<0.05 to NM and pCRC CD20 IM 20 39p<0.05 to pCRC 20 33 CD20 OM 137 327p<0.05 to pCRC 134 303p<0.05 to pCRC CD20 PT 153 224 196 213 Citation Format: Andriy Trailin, Wenjing Ye, Esraa Ali, Sergii Pavlov, Lenka Cervenkova, Filip Ambrozkiewicz, Ondrej Vycital, Ondrej Daum, Vaclav Liska, Kari Hemminki. Adaptive immune cells in colorectal cancer between normal mucosa, primary tumor and liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5528.