Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Oncoimmunology. 2022 Apr 14;11(1):2054757. doi: 10.1080/2162402X.2022.2054757. eCollection 2022.
Colon tumors with deficient DNA mismatch repair (dMMR) are generally infiltrated by T cells more densely than tumors with proficient mismatch repair (pMMR). However, high numbers of tumor-infiltrating lymphocytes (TILs) are found in select pMMR tumors, and low numbers of TILs are seen in select dMMR tumors. In this study, we compared T-cell repertoires in 20 pMMR and 27 dMMR colon tumors with high and low TIL counts. We found that T cells in dMMR tumors are more clonal and their repertoire is less rich compared with T cells in pMMR tumors. In the dMMR group, T cells in TIL-high tumors were more clonal and their repertoire was less rich compared with T cells in TIL-low tumors, but in the pMMR group, T-cell diversity in TIL-high tumors was comparable to T-cell diversity in TIL-low tumors. These findings suggest that T cells clonally expand in dMMR tumors, possibly in response to MMR deficiency-induced tumor neoantigens.
与错配修复功能完整（pMMR）的肿瘤相比，错配修复功能缺陷（dMMR）的结肠肿瘤通常有更密集的 T 细胞浸润。然而，在一些 pMMR 肿瘤中也发现了大量的肿瘤浸润淋巴细胞（TIL），而在一些 dMMR 肿瘤中则发现了少量的 TIL。在这项研究中，我们比较了 20 例高 TIL 计数和 27 例低 TIL 计数的 pMMR 和 dMMR 结肠肿瘤中的 T 细胞受体库。我们发现，与 pMMR 肿瘤中的 T 细胞相比，dMMR 肿瘤中的 T 细胞更具克隆性，其受体库也不那么丰富。在 dMMR 组中，TIL 高肿瘤中的 T 细胞比 TIL 低肿瘤中的 T 细胞更具克隆性，其受体库也不那么丰富，但在 pMMR 组中，TIL 高肿瘤中的 T 细胞多样性与 TIL 低肿瘤中的 T 细胞多样性相当。这些发现表明，T 细胞在 dMMR 肿瘤中克隆性扩增，可能是对 MMR 缺陷诱导的肿瘤新抗原的反应。
