Reference SummaryYou S, Cancer Cell 2024 Aug 12;42(8):1415-1433.e12
Title |
Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity. |
Authors |
You S; Li S; Zeng L; Song J; Li Z; Li W; Ni H; Xiao X; Deng W; Li H; Lin W; Liang C; Zheng Y; Cheng SC; Xiao N; Tong M; Yu R; Huang J; Huang H; Xu H; Han J; Ren J; Mao K |
Journal |
Cancer Cell |
Volume |
42 |
Issue |
8 |
Year |
2024 |
Pages |
1415-1433.e12 |
Abstract |
The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses. |
Links |
J:352967 – MGI References 39029466 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed - 100 |
||
| C57BL/6-Apctm1Tyj/+ Tg(Vil1-cre)997Gum | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| C57BL/6-ApcMin/+ Foxp3tm3(HBEGF/GFP)Ayr/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| C57BL/6-ApcMin/+ Foxp3tm3(HBEGF/GFP)Ayr/+ | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
observed |
|
| C57BL/6-ApcMin/+ Tcratm1Mom | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed - 100 |
||
| C57BL/6-ApcMin/+ Tcratm1Mom | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
18 |
|
| C57BL/6-ApcMin/+ Ccl22em2Tshu/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon tumor |
|
Intestine - Large Intestine - Colon |
observed |
|
| C57BL/6-ApcMin/+ Ccr4em2Gpt/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed - 89 |
||
| C57BL/6-ApcMin Ccr4em2Gpt | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
observed - 56 |
||
| C57BL/6-ApcMin/+ Ccr4em1Gpt | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
100 |
||
| C57BL/6-ApcMin/+ Ccr4em1Gpt Foxp3tm4(YFP/icre)Ayr/+ | Intestine - Large Intestine - Colon tumor | Intestine - Large Intestine - Colon |
33 |
||
| C57BL/6J-ApcMin/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed - 100 |
||
| C57BL/6-ApcMin/+ Tcratm1Mom | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed - 100 |
||
| C57BL/6-ApcMin/+ Tcratm1Mom | Intestine - Small Intestine tumor |
|
Intestine - Small Intestine |
100 |
|
| C57BL/6-ApcMin/+ Ccr4em2Gpt/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed - 100 |
||
| C57BL/6-ApcMin Ccr4em2Gpt | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed - 100 |
||
| C57BL/6-ApcMin/+ Ccr4em1Gpt | Intestine - Small Intestine tumor | Intestine - Small Intestine |
100 |
||
| C57BL/6-ApcMin/+ Ccr4em1Gpt Foxp3tm4(YFP/icre)Ayr/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
100 |
||
| C57BL/6J-ApcMin/+ | Intestine tumor | Intestine |
observed |
||
| C57BL/6-ApcMin/+ Ccl22em2Tshu/+ Tg(Nr4a1-EGFP/cre)820Khog | Intestine tumor | Intestine |
observed |
||
| C57BL/6J-ApcMin/+ | Intestine tumor |
|
Intestine |
observed |
|
| C57BL/6-ApcMin/+ Foxp3tm3(HBEGF/GFP)Ayr/+ | Intestine tumor | Intestine |
observed |