journal article·2026-01Open access

Targeting the Dynamics Between TAMs and CAR‐T Cells in Solid Tumor Therapies

Xiang Zhang, Hao Zheng, Zi‐Chang Liu, Ling‐Jie Luo, Xiao Dong, Xin‐Gang Cui, Yan‐Wei Wu, Liang Chen

Advanced Science· Volume 13· Issue 1

Abstract

Abstract Although CAR T‐cell therapy has transformed treatment outcomes for patients with haematological malignancies, the existing barriers in solid tumors treatment remain due to TAM immunosuppression. This review explores the work of others on the interplay between M2‐like immunosuppressive TAMs and CAR‐T cells in the tumor microenvironment. The ways TAMs impair the effector functions of CAR‐T cells are described mediated by secretion of cytokines, immune checkpoints, metabolites, and detrimental post‐translational modification. New concept therapeutic approaches are designed to these interactions for improving the efficacy of CAR‐T cells in solid tumors. With an emphasis on novel strategies to counteract TAM immunosuppression, this review aims to reshape the perspective on the utility and effectiveness of CAR‐T therapy in solid tumors and, consequently, extend the reach of a highly promising therapeutic approach.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: CAR-T cell therapy research · Immunotherapy and Immune Responses · Immune Cell Function and Interaction

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Medicine Shanghai University Shanghai 200444 China

Department of Urology, Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200092 China

Shanghai Tenth People's Hospital Shanghai 200072 China

Institute of Artificial Intelligence and Biomanufacturing Shanghai University Shanghai 200444 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China

References (100+)

Show source-provided references
1. 10.1038/s41551-018-0235-910.1038/s41551-018-0235-9 ↗
2. 10.1038/s41408-021-00459-710.1038/s41408-021-00459-7 ↗
3. 10.1186/s13045-020-00890-610.1186/s13045-020-00890-6 ↗
4. 10.1038/s41408-020-00346-710.1038/s41408-020-00346-7 ↗
5. 10.1182/bloodadvances.202000146610.1182/bloodadvances.2020001466 ↗
6. 10.1038/s41408-024-01191-810.1038/s41408-024-01191-8 ↗
7. 10.1186/s12943-024-02079-810.1186/s12943-024-02079-8 ↗
8. 10.1038/s41423-021-00655-210.1038/s41423-021-00655-2 ↗
9. Cho Y. · Trends Immunol. · 2024
10. 10.1016/j.ccell.2020.07.01310.1016/j.ccell.2020.07.013 ↗
11. 10.1016/j.canlet.2015.10.02210.1016/j.canlet.2015.10.022 ↗
12. 10.7150/thno.3071610.7150/thno.30716 ↗
13. 10.7150/thno.5092810.7150/thno.50928 ↗
14. 10.1002/mco2.65810.1002/mco2.658 ↗
15. 10.1038/s41392-025-02325-510.1038/s41392-025-02325-5 ↗
16. 10.1186/s13046-023-02832-910.1186/s13046-023-02832-9 ↗
17. 10.7150/ijbs.2983610.7150/ijbs.29836 ↗
18. 10.1038/s41423-019-0271-810.1038/s41423-019-0271-8 ↗
19. 10.1016/j.ymthe.2025.03.00510.1016/j.ymthe.2025.03.005 ↗
20. 10.7150/ijbs.10803610.7150/ijbs.108036 ↗
21. 10.1038/s41392-025-02387-510.1038/s41392-025-02387-5 ↗
22. 10.1016/j.tips.2024.03.00410.1016/j.tips.2024.03.004 ↗
23. 10.3389/fimmu.2025.154823410.3389/fimmu.2025.1548234 ↗
24. 10.1186/s12943-025-02255-410.1186/s12943-025-02255-4 ↗
25. 10.1016/j.critrevonc.2025.10472910.1016/j.critrevonc.2025.104729 ↗
26. 10.1016/j.jhep.2006.09.01410.1016/j.jhep.2006.09.014 ↗
27. 10.1080/19490976.2024.236302010.1080/19490976.2024.2363020 ↗
28. 10.1146/annurev-immunol-101220-02345810.1146/annurev-immunol-101220-023458 ↗
29. 10.1038/s41591-018-0036-410.1038/s41591-018-0036-4 ↗
30. 10.1038/s41591-018-0041-710.1038/s41591-018-0041-7 ↗
31. 10.1038/s41423-019-0306-110.1038/s41423-019-0306-1 ↗
32. 10.1186/s12943-023-01830-x10.1186/s12943-023-01830-x ↗
33. Li Y.‐R. · Med · 2025
34. 10.1158/0008-5472.CAN-23-103810.1158/0008-5472.CAN-23-1038 ↗
35. 10.3389/fimmu.2017.0081510.3389/fimmu.2017.00815 ↗
36. 10.1172/JCI8945510.1172/JCI89455 ↗
37. 10.7150/thno.5374910.7150/thno.53749 ↗
38. 10.1038/s42255-024-00976-210.1038/s42255-024-00976-2 ↗
39. 10.1016/j.ymthe.2021.10.00410.1016/j.ymthe.2021.10.004 ↗
40. 10.1136/jitc-2021-00335410.1136/jitc-2021-003354 ↗
41. 10.1136/jitc-2022-00634310.1136/jitc-2022-006343 ↗
42. 10.1186/s13046-021-01873-210.1186/s13046-021-01873-2 ↗
43. Prinz L. F. · Cell Rep. Med. · 2024 · 5
44. 10.1182/blood.202402544010.1182/blood.2024025440 ↗
45. 10.1016/j.cell.2023.06.00210.1016/j.cell.2023.06.002 ↗
46. 10.1038/s41577-021-00566-310.1038/s41577-021-00566-3 ↗
47. 10.1186/s13046-023-02845-410.1186/s13046-023-02845-4 ↗
48. 10.1016/j.immuni.2016.06.02010.1016/j.immuni.2016.06.020 ↗
49. 10.1038/s41571-023-00729-210.1038/s41571-023-00729-2 ↗
50. 10.1038/s41571-023-00813-710.1038/s41571-023-00813-7 ↗
51. 10.1016/j.jaci.2009.09.01710.1016/j.jaci.2009.09.017 ↗
52. 10.1038/s41388-021-01946-810.1038/s41388-021-01946-8 ↗
53. 10.1111/j.1600-065X.2008.00760.x10.1111/j.1600-065X.2008.00760.x ↗
54. 10.1038/s41388-020-01501-x10.1038/s41388-020-01501-x ↗
55. 10.1038/cddis.2015.16210.1038/cddis.2015.162 ↗
56. 10.1186/s40164-024-00552-010.1186/s40164-024-00552-0 ↗
57. Amit S. · 2003 · 15
58. 10.1158/0008-5472.CAN-22-373910.1158/0008-5472.CAN-22-3739 ↗
59. 10.1111/imr.1230310.1111/imr.12303 ↗
60. 10.1016/j.trecan.2020.04.00310.1016/j.trecan.2020.04.003 ↗
61. 10.1016/0092-8674(95)90322-410.1016/0092-8674(95)90322-4 ↗
62. 10.1007/s13238-020-00694-x10.1007/s13238-020-00694-x ↗
63. 10.1016/j.cell.2004.05.02310.1016/j.cell.2004.05.023 ↗
64. 10.1158/1078-0432.CCR-09-101510.1158/1078-0432.CCR-09-1015 ↗
65. 10.1016/j.lfs.2024.12305910.1016/j.lfs.2024.123059 ↗
66. 10.1182/blood-2023-18646510.1182/blood-2023-186465 ↗
67. 10.1038/s41467-022-31035-710.1038/s41467-022-31035-7 ↗
68. 10.1186/s13045-019-0831-510.1186/s13045-019-0831-5 ↗
69. 10.3390/cells1005125210.3390/cells10051252 ↗
70. Niu Q. · Mol. Ther. · 2024
71. 10.3390/ijms2209460010.3390/ijms22094600 ↗
72. 10.1158/2326-6066.CIR-22-038710.1158/2326-6066.CIR-22-0387 ↗
73. 10.1073/pnas.172245211510.1073/pnas.1722452115 ↗
74. 10.1161/CIRCRESAHA.107.15587910.1161/CIRCRESAHA.107.155879 ↗
75. 10.1158/0008-5472.CAN-21-123710.1158/0008-5472.CAN-21-1237 ↗
76. 10.1002/hep.2470010.1002/hep.24700 ↗
77. 10.3390/cells1010270010.3390/cells10102700 ↗
78. 10.3389/fcell.2025.167633810.3389/fcell.2025.1676338 ↗
79. 10.3389/fimmu.2025.152984710.3389/fimmu.2025.1529847 ↗
80. 10.1186/s13287-024-04061-z10.1186/s13287-024-04061-z ↗
81. 10.1186/s12967-023-04575-910.1186/s12967-023-04575-9 ↗
82. 10.1038/s41467-021-20893-210.1038/s41467-021-20893-2 ↗
83. 10.15252/emmm.20211450210.15252/emmm.202114502 ↗
84. 10.1038/s41587-020-0462-y10.1038/s41587-020-0462-y ↗
85. 10.1038/nm.333710.1038/nm.3337 ↗
86. 10.1016/j.jconrel.2020.07.00110.1016/j.jconrel.2020.07.001 ↗
87. 10.3389/fimmu.2025.157303910.3389/fimmu.2025.1573039 ↗
88. 10.1126/sciimmunol.abq301610.1126/sciimmunol.abq3016 ↗
89. 10.3389/fimmu.2022.97619610.3389/fimmu.2022.976196 ↗
90. 10.1186/s12929-022-00893-010.1186/s12929-022-00893-0 ↗
91. 10.1186/s40425-017-0257-y10.1186/s40425-017-0257-y ↗
92. 10.1158/0008-5472.CAN-14-099210.1158/0008-5472.CAN-14-0992 ↗
93. 10.1136/gutjnl-2015-31051410.1136/gutjnl-2015-310514 ↗
94. 10.1038/nature1013810.1038/nature10138 ↗
95. 10.1016/S1470-2045(16)00078-410.1016/S1470-2045(16)00078-4 ↗
96. 10.1158/1078-0432.CCR-18-113310.1158/1078-0432.CCR-18-1133 ↗
97. 10.1158/1535-7163.MCT-20-096110.1158/1535-7163.MCT-20-0961 ↗
98. 10.1038/s41591-021-01497-110.1038/s41591-021-01497-1 ↗
99. 10.7150/thno.4399110.7150/thno.43991 ↗
100. 10.7150/ijbs.6318110.7150/ijbs.63181 ↗