Immune biomarkers for predicting response to adoptive cell transfer as cancer treatment

Abstract

Adoptive cell transfer (ACT) is a form of personalised immunotherapy which has shown promising results in metastasised cancer. For this treatment, autologous T lymphocytes are selected and stimulated in vitro before re-administration in large numbers. However, only a fraction of patients benefit from ACT, and it is not yet known what biomarkers can predict treatment outcome. In this review, we describe what tumour characteristics are associated with response to ACT. Based on the current knowledge, the best candidate biomarker for a good anti-tumour response seems to be a large number of neoantigens with a homogeneous distribution across the tumour in combination with sufficient MHC-I expression level. Additionally, it is necessary to be able to isolate a diverse population of T cells reactive to these neoantigens from tumour tissue or peripheral blood. Additional promising candidate biomarkers shared with other cancer immunotherapies are a large number of tumour-infiltrating cytotoxic and memory T cells, normal levels of glycolysis, and a pro-inflammatory cytokine profile within the tumour. Intense research in this field will hopefully result in identification of more biomarkers for cancers with low mutational load.

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

“…TSAs result from the accumulation of mutations within a tumor cell line (19,37). A special category of these antigens comprises neoantigens, which are present on MHC molecules (38,39) (Figure 1). Surprisingly, neoantigens are unique to the patient rather than to the tumor, and are often downregulated in tumors, suggesting that tumors evade immune destruction (40)(41)(42)(43)(44)(45).…”

A Palette of Cytokines to Measure Anti-Tumor Efficacy of T Cell-Based Therapeutics

“…Showing the ability of antigen specific Th1 cells through the use of adhesion molecules places the Th1 subset at the forefront of tumor rejection activity [ 17 ]. Th1 cells primarily stimulate CTL activation and differentiation and the secretion of cytokines such as IL-2, IL-12, IFN-γ, and TNF-α support CTL effector phenotype [ 20 ]. Additionally, Th1 therapy can induce lasting immunological memory to revive CTL generation upon tumor recurrence [ 17 ].…”

“…Critical to this work is the discovery that Th1 cells expressed adhesion molecules LFA-1/ICAM-1 [ 19 ], that allow transmigration into tumor tissues across tumor vessels, supporting tumor metastasis [ 17 , 19 ]. The cytokines secreted by Th1 T cells are commonly associated with a good prognosis for anti-tumor therapies [ 20 ]. Moreover, Th1 cytokines produced upon antigen stimulation directly induce the recruitment of effector cells such as CD8 + T cells, NKT cells, and NK cells to the tumor [ 17 ].…”

Kynurenic acid and cancer: facts and controversies

“…Taking into consideration an anti-inflammatory potential of KYNA, this compound may be considered as a potent anticancer agent since continuous inflammation is one of the factors which may induce process of carcinogenesis [103,104]. On the other hand, the proper immune response may inhibit the early stages of carcinogenesis or prevent spreading of cancer cells into the whole body [105,106].…”