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Cancer immunotherapy, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy, has revolutionized the paradigm in cancer treatment. However, the clinical outcome of immunotherapy varies considerably among patients and only a minority of patients achieve long-term clinical benefits. This is largely attributed to the fact that existing cancer immunotherapies, which concentrate on several classical targets (CTAL-4, PD-1/PD-L1, etc.) and limited types of immune cell populations (T cells), are insufficient to cope with the complexity of highly heterogeneous tumor microenvironment (TME). This calls for more efforts to not only expand our toolbox for manipulating anticancer immunity but also diversify our combinational strategies. To this end, it is urgent to deeper our understanding of cancer immunotherapy by using both experimental and computational methodologies from multi-scale perspectives: 1) novel targets from either tumor cells or non-tumor cells within TME (e.g., tumor intrinsic resistance drivers, new immune checkpoints, neoantigens), 2) in-depth characterization of more immune cell populations (e.g., macrophages, Tregs, B cells) and their interactions and dynamics within TME, 3) landscape of actionable targets in patient populations for combination design. These efforts will open the avenue of rational design of combinational immunotherapies, allowing researchers and clinicians to design novel targeting therapeutics or to optimally orchestrate combinatory strategies aiming to surmount resistance mechanisms and improve clinical outcomes.

This Research Topic aims at inspiring novel insights into the cancer immunity mechanisms, novel therapeutic targets, and effective combinational strategies of cancer immunotherapies. We welcome Original Research articles, Review articles, Mini Reviews, Case Reports, Clinical Trials, and Perspectives that address the fundamental understanding of mechanisms underlying cancer immunotherapy, as well as the therapeutic potential of novel combinational therapy.

Submissions may focus on, but are not limited to, the following subtopics:

1. Primary or acquired resistance mechanisms of cancer immunotherapies

2. Single-cell characterization of dynamic immune response

3. Mechanistic research targeting cytokines and signaling pathways within the tumor that lead to activation or inhibition of anti-tumor immunity

4. Multifunctional antibody/protein or engineered immune cells with potent efficacy

5. Novel cancer immunotherapy insights mining from Omics big data by interdisciplinary strategies such as computational biology, bioinformatics, and artificial intelligence

6. Case reports and clinical trials of new combinatory strategies for cancer treatment

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