Tran Kelly, Kumari Anita N, Raghu Dinesh, Cox Daniel R A, Goh Su Kah, Perini Marcos V, Muralidharan Vijayaragavan, Tebbutt Niall C, Behren Andreas, Mariadason John, Williams David S, Mielke Lisa A
Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
School of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australia.
iScience. 2024 Aug 22;27(9):110754. doi: 10.1016/j.isci.2024.110754. eCollection 2024 Sep 20.
The presence of precursor to exhausted (T) CD8 T cells is important to maintain robust immunity following treatment with immune checkpoint inhibition (ICI). Impressive responses to ICI are emerging in patients with stage II-III mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC). We found 64% of dMMR and 15% of mismatch repair-proficient (pMMR) stage III CRCs had a high frequency of tumor infiltrating lymphocytes (TIL-hi). Furthermore, expression of TCF-1 by CD8 T cells predicted improved patient prognosis and T cells (CD3CD8TCF-1PD-1) were abundant within lymphoid aggregates of stage III CRCs. In contrast, CD3CD8TCF-1PD-1 cells were more abundant at the invasive front and tumor core, while γδ T cells were equally abundant in all tumor areas. Interestingly, no differences in the frequency of T cells were observed between TIL-hi dMMR and TIL-hi pMMR CRCs. Therefore, T cell function and ICI response rates in TIL-hi CRC warrants further investigation.
耗竭前（T）CD8 T细胞的存在对于免疫检查点抑制（ICI）治疗后维持强大的免疫力很重要。II-III期错配修复（MMR）缺陷（dMMR）结直肠癌（CRC）患者对ICI出现了令人印象深刻的反应。我们发现，64%的dMMR和15%的错配修复 proficient（pMMR）III期CRC具有高频率的肿瘤浸润淋巴细胞（TIL-hi）。此外，CD8 T细胞表达TCF-1预示着患者预后改善，并且T细胞（CD3CD8TCF-1PD-1）在III期CRC的淋巴样聚集物中丰富。相比之下，CD3CD8TCF-1PD-1细胞在侵袭前沿和肿瘤核心更为丰富，而γδ T细胞在所有肿瘤区域的丰度相同。有趣的是，在TIL-hi dMMR和TIL-hi pMMR CRC之间未观察到T细胞频率的差异。因此，TIL-hi CRC中的T细胞功能和ICI反应率值得进一步研究。
