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Featured Publications

See below for some of the most recent publications from the Brooks lab. Showcasing the exciting and cutting edge research being done in the lab

Regulation and impact of tumor-specific CD4+ T cells in cancer and immunotherapy

Guo M, Liu MYR, Brooks DG. Regulation and impact of tumor-specific CD4+ T cells in cancer and immunotherapy. Trends Immunol. 2024 Mar 19:S1471-4906(24)00030-9. doi: 10.1016/j.it.2024.02.005. Epub ahead of print. PMID: 38508931.

Figure 2- v5.jpg

Highlights

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  • Suboptimal CD4  +  T cell activation leads to a hyporesponsive state in mice characterized by incomplete differentiation, limited cytokine production, and changes in T helper (Th) subsets. Together, these factors impair CD4  +  T cell trafficking to the tumor and enable the immune evasion of tumor cells.

  • Sustained inflammation, antigen stimulation, and suppressive factors induce CD4  +  T cell dysfunctions during tumor progression in murine models.

  • Since CD4  +  T cells can help multiple parameters of the innate and adaptive immune response, reinvigorating CD4  +  T cells holds great potential in enhancing various immunotherapies, including immune checkpoint blockade, cancer vaccines, and the use of CAR T cells.

Keywords:

CD4+ T cell, cancer, Tumor immunology, dysfunction, exhaustion, immunotherapy, T regulatory cell, antigen presenting cell, CD8 T cell

Pubmed

Molecular, metabolic, and functional CD4 T cell paralysis in the lymph node impedes tumor control

Guo M, Abd-Rabbo D, Bertol BC, Carew M, Lukhele S, Snell LM, Xu W, Boukhaled GM, Elsaesser H, Halaby MJ, Hirano N, McGaha TL, Brooks DG. Molecular, metabolic, and functional CD4 T cell paralysis in the lymph node impedes tumor control. Cell Rep. 2023 Aug 30;42(9):113047. doi: 10.1016/j.celrep.2023.113047. Epub ahead of print. PMID: 37651234.

Graphical abstract for CD4 T cell and Cancer paper Mengdi Guo

Highlights

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  • CD4 TTS cells are primed but rapidly “paralyzed” in the dLN during tumor development

  • Tregs and CTLA4 halt CD4 TTS cell activation, freezing proliferation, and differentiation

  • CD4 TTS cells retain latent functional capacity to resume tumor infiltration

  • Overcoming CD4 TTS cells paralysis enhances long-term tumor control

Keywords:

cancer, tumor, immunology, CD4 T cell, dysfunction, exhaustion, immunotherapy, CTLA4, T regulatory cell, metabolism, transcriptomic signature

Pubmed

The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity

Lukhele S, Rabbo DA, Guo M, Shen J, Elsaesser HJ, Quevedo R, Carew M, Gadalla R, Snell LM, Mahesh L, Ciudad MT, Snow BE, You-Ten A, Haight J, Wakeham A, Ohashi PS, Mak TW, Cui W, McGaha TL, Brooks DG. The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity. Immunity. 2022 Dec 13;55(12):2369-2385.e10. doi: 10.1016/j.immuni.2022.10.020. Epub 2022 Nov 11. PMID: 36370712; PMCID: PMC9809269.

Graphical abstract to IRF2 CD8 exhaustion paper Sabelo Lukhele

Highlights

 

  • IRF2 expression by CD8+ TILs drives T cell exhaustion

  • IRF2 drives the suppressive program induced by interferons

  • IRF2 deletion enables CD8+ T cell-driven control of multiple tumor types

  • IRF2 deficiency boosts efficacy of adoptive cell and immune checkpoint therapies

Keywords:  

interferon regulatory factor 2, IRF2, type I interferon, interferon gamma, CD8+ T cells, T cell,  exhaustion, cancer, immunotherapy, adoptive cell transfer,  CyTOF

Pubmed

Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy

Boukhaled GM, Gadalla R, Elsaesser HJ, Abd-Rabbo D, Quevedo R, Yang SYC, Guo M, Wang BX, Noamani B, Gray D, Lau SCM, Taylor K, Aung K, Spreafico A, Hansen AR, Saibil SD, Hirano N, Guidos C, Pugh TJ, McGaha TL, Ohashi PS, Sacher AG, Butler MO, Brooks DG. Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy. Nat Immunol. 2022 Aug;23(8):1273-1283. doi: 10.1038/s41590-022-01262-7. Epub 2022 Jul 14. PMID: 35835962.

Figure 2 from PD1 blockage Type 1 interferon in human clinical trial paper Giselle Boukhaled

Highlights

 

  • The response of circulating effector CD4 T cells to type I interferons (IFN-I) correlates with the overall survival of patients with cancer receiving immune checkpoint inhibition. 

  • IFN-I responsiveness is already epigenetically encoded before treatment initiation, highlighting a deterministic, clinically relevant feature that can predict therapeutic efficacy.

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Pubmed

Dynamic CD4+ T cell heterogeneity defines subset-specific suppression and PD-L1-blockade-driven functional restoration in chronic infection

Snell LM, Xu W, Abd-Rabbo D, Boukhaled G, Guo M, Macleod BL, Elsaesser HJ, Hezaveh K, Alsahafi N, Lukhele S, Nejat S, Prabhakaran R, Epelman S, McGaha TL, Brooks DG. Dynamic CD4+ T cell heterogeneity defines subset-specific suppression and PD-L1-blockade-driven functional restoration in chronic infection. Nat Immunol. 2021 Dec;22(12):1524-1537. doi: 10.1038/s41590-021-01060-7. Epub 2021 Nov 18. PMID: 34795443; PMCID: PMC10286806.

Figure 1 from CD4 PDL1 paper Laura Snell

Highlights

 

  • PDL1 suppresses Th1 amplification, prevents Th1 cytokine production and abolishes CD4 CTL killing capacity during chronic viral infection

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Pubmed
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