Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy

Abstract

As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy. Such interrogation of the tumor, blood, and host immune parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. To approach these opportunities for progress, the Society for Immunotherapy of Cancer (SITC) reconvened the Immune Biomarkers Task Force. Comprised of an international multidisciplinary panel of experts, Working Group 4 sought to make recommendations that focus on the complexity of the tumor microenvironment, with its diversity of immune genes, proteins, cells, and pathways naturally present at baseline and in circulation, and novel tools to aid in such broad analyses.

RNA-seq for identification of therapeutically targetable determinants of immune activation in human glioblastoma

“…Immunotherapy, led by programmed cell death-1 / programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint blockade, has dramatically altered the landscape of cancer treatment in multiple tumor types [1]. However, despite promise in preclinical and early phase studies [2,3], single agent programmed death 1 (PD-1) inhibition is ineffective for recurrent GBM in the absence of a rare, markedly hypermutated tumor [4–6].…”

CyTOF Measurement of Immunocompetence Across Major Immune Cell Types

“…But these can lead to autoimmune syndromes on one hand, and lack efficacy in certain patients on the other hand. Better understanding of the immune landscape prior to (and during) treatment is needed to allow tailoring of these therapies (Gnjatic et al, 2017). In fact, one could argue that accurate assessment of immune competence could benefit many areas of clinical medicine, since the immune system is central not only to cancer and transplant rejection, but also plays a major role in cardiovascular disease, infection, and autoimmunity, for example.…”

Discovery and application of immune biomarkers for hematological malignancies

“…Compelling evidence indicates that pre-existing immunological features contribute to the ability of patients with solid tumours to respond to immunotherapy with immunomodulatory agents such as checkpoint inhibitors [2]. The Immune Biomarkers Task Force of the Society for Immunotherapy of Cancer (SITC) recently published recommendations on the discovery of immune-related biomarkers, in which it highlighted the complexity of the tumour microenvironment (TME) and discussed novel tools to analyse the diversity of immune genes, proteins, cells and pathways [3]. A broader understanding of baseline immunity, both in the periphery and in the TME, and of immune escape mechanisms is likely to expedite the identification of biomarkers that are predictive of clinical outcome and elucidate why cancer patients might fail to respond to immunotherapy [4,5].…”