Immuno-Monitoring of Cancer Immunotherapy

Dear Colleagues,

In the past decade, tumor-targeting immunotherapies have been developed for many human cancers, including colorectal carcinoma, ovarian carcinoma, melanoma, prostate cancer, glioblastoma, lung carcinoma and hepatocellular carcinoma, and so on. The most widely employed strategies are immune checkpoint blockade, hematopoietic stem cell transplantation, anti-tumor monoclonal antibodies and adoptive transfer of chimeric antigen receptor (CAR) T cells, although many other approaches are now being developed. Immunotherapy as a treatment for cancer is based on the premise that the patient’s own immune system can be activated in a manner that eliminates the pre-existing cancer. Many immunotherapy trials are accompanied by immune monitoring, which can provide crucial insights into immune cell behavior at both population as well as single-cell levels. The immune system is a complex, multifaceted network that is not fully understood. Monitoring immune responses is essential for rational cancer immunotherapy development. The primary objectives of immune monitoring after immunotherapy are to document the induction of tumor-specific immune responses and to correlate the presence and magnitude of immunotherapy induced immune responses to clinical outcomes. Immune monitoring could also be used to (1) define the ability of a given therapy to generate tumor associated antigen-specific immune responses, (2) compare among therapies of different potencies, (3) define the ability of a given therapy to generate antigen-cascade responses, (4) define the ability of a given cytokine, drug, etc. to enhance or hinder immune responses, (5) define the appropriate populations for the therapy studies and (6) define the presence and activity of inhibitory/suppressor cell populations. Despite advances in the development of immune monitoring assays, it has been difficult to establish significant correlations between therapy-induced immune responses and clinical outcomes. This lack of correlation could reflect the methodological limitations of immunologic assays or the post therapeutic absence of antitumor responses sufficiently robust to induce tumor free or overall survival. A wide portfolio of monitoring assays are currently available. They are being investigated for the ability to define surrogate markers that could be used as predictor of clinical response and thus serve to advance immunotherapy development. Immune responses against cancer induced by immunotherapy are likely a balanced between immune responses of various subsets of both effectors and suppressors. The main focus of this Special Issue will be on the current immune monitoring assays, their strength and weakness and their applications in recent immunotherapy clinical trials. We are particularly interested in manuscript that report on immune monitoring assays on cancer immunotherapy trials with clinical effective therapy or novel immune assays applied in clinical trials of all stages. Assays for monitoring innate immunity and adaptive immunity pre and post therapy will be discussed in this Special Issue.

Potential topics include but are not limited to:

1. Assessment of correlation between immune responses and clinical responses.
2. Quality control/quality assurance/standardization/harmonization and rigorous validation studies that must be performed to establish proper experimental and analytical immune monitoring methods.
3. Evaluating the potency of cancer immunotherapy: Regulators of immune responses (regulatory T cells, myeloid-derived suppressor cells, NTK, etc.)
4. Innate immune responses (NK cell, NKG2D, sMICA).
5. Immune monitoring for cancer immunotherapy using checkpoint inhibitors: blood-based biomarkers measurements (regulatory T cells, myeloid-derived suppressor cells, neutrophil/lymphocyte ratio, absolute lymphocyte count, ICOS, etc.).
6. Tumor microenvironment immune monitoring (immunoscore, immune subsets such as M1 and M2, gene expression profiles).
7. Next-generation immune monitoring technologies: Mass cytometry, microfluidic tools for whole-blood immunoassays of plasma components and functional immunoassays, analysis of T-cell receptor clonotypes of patient PBMCs pre- and post-immunotherapy.

Dr. Kwong Tsang
Dr. Massimo Fantini
Dr. Philip M Arlen
Dr. Christina M. Annunziata
Dr. Takuya Tsunoda
Guest Editors

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