The Tumor Microenvironment - Optimize your T Cell Marker Research with Bethyl Antibodies

Rapid progress in the field of cancer immunotherapy is a result of advances in our understanding of immune marker expression, antigen presentation, and the cell-mediated immune response involving CD3+ T-lymphocytes. T-cells are crucial to the body’s immune response to cancer, both endogenously and following therapeutic intervention. A T-cell marker panel that can identify subsets of tumor-associated T-cells allows scientists to identify and target subpopulations of T-cells playing unique roles in the immune response against a tumor.

CD4+ and CD8+ T-cells participate in the anti-tumor immune response at the site of the tumor or in the periphery, such as in tumor-draining lymph nodes. Among the T-cells localized to the tumor, some enter the tumor as naïve cells and undergo maturation within the tumor [1]. Others are primed in the periphery and subsequently traffic to the site of the tumor to participate in the effector or memory response against an established tumor [2]. Adhesion molecules including CD31 [3], CD43 [4] and CD44 [5] help regulate the migration of these T-cells.

Within the tumor microenvironment, a positive prognosis is usually conferred to patients bearing solid tumors with a high CD8+ T-cell infiltrate [6], as tumor-infiltrating cytotoxic T-cells are the crucial mediator of anti-tumor immune responses. However, CD8+ T-cell activity can be regulated within the tumor microenvironment. Myeloid cells, CD4+ helper T-cells, and tumor cells can modulate the level of both maturation and activation of a CD8+ T-cell. Among many, T-cell exhaustion and anergy are major challenges to the maintenance of anti-tumor immune responses [7] and can be monitored via changes to cell surface molecules.

In parallel, CD4+ T-cells can support an ongoing immune response against solid tumors through the promotion of a Th1-skewed microenvironment that primes CD8+ T-cells. Th17-polarized CD4+ T-cells, too, have recently been shown in mouse models to promote anti-tumor immune responses, possibly due to their memory-like phenotype. However, depending on both the type of cancer and the phenotype of the T-cells, CD4+ T-cells may confer either a positive or negative prognosis. While helper and memory CD4+ T-cells bolster the inflammatory response, regulatory T-cells suppress ongoing immune responses and can promote tumor progression [8].

T-cell marker research is crucial to our understanding of how the immune response to a tumor is affected. Being able to categorize subsets of T-cells based on their physiologic localization and maturation state in a variety of human cancer types and corresponding mouse models will improve the ability to target crucial T-cell subsets for activation or inhibition at different stages of tumor progression. Additionally, characterizing molecules that may function as novel immune checkpoints or exhaustion markers within the context of cancer, including CD5 [9] and CD8, can build on the successes of anti-CTLA4 and anti-PD-1 therapies, translating this field into the clinic yet again.

Our current T-cell marker portfolio consists of these polyclonal and monoclonal – including our new recombinant rabbit monoclonal antibodies (RmAbs) products:

 

CD247 CD43 CD8 GATA
CD28 CD45 CD8a SMAD3
CD31 CD45 RmAb EOMES SMAD4
CD3E RmAb CD5 FOXO3a STAT5a
CD4 RmAb CD7 FOXP3 TBX21

 

T-Cell Regulation/Immune Checkpoints 

PD-L1 LAG3 CD137
PD-1 GITR CD40
TIGIT TIM3 B7-H3
VISTA OX40 B7-H4

 

References

1 Sautès-Fridman C, Lawand M, Giraldo NA, Kaplon H, Germain C, Fridman WH, Dieu-Nosjean MC. 2016. Tertiary Lymphoid Structures in Cancers: Prognostic Value, Regulation, and Manipulation for Therapeutic Intervention. Front. Immunol. 7, 407.

2 Slaney CY, Kershaw MH, Darcy PK. 2014. Trafficking of T Cells into Tumors. Cancer Res. 74(24). 7168-7174.

3 Marelli-Berg FM, Clement M, Mauro C, Caligiuri G. 2013. An immunologist’s guide to CD31 function in T-cells. J Cell Sci 126, 2343-2352.

4 Mody PD, Cannon JL, Bandukwala HS, Blaine KM, Schilling AB, Swier K, Sperling AI. 2007. Signaling through CD43 regulates CD4 T-cell trafficking. Blood. 110(8), 2974-2982.

5 Baaten BJ, Li CR, Bradley LM. 2010. Multifaceted regulation of T cells by CD44. Commun Integr Biol. 3(6), 508-512.

6 Fridman WH, Pagès F, Sautès-Fridman C, Galon J. 2012. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12, 298-306.