Adaptations and Advancement of Biologic Immunotherapy in the Management of Immunologically Cold Solid Malignancies

Abstract

Contemporary breakthroughs within cancer immunotherapy are frequently cited amongst the most promising of therapeutic directions for medical oncology and perioperative solid tumour management. However to date, the efficacy of treatment of immunologically derived therapeutic modalities is limited to a few highly selective malignancies, exemplified by leukaemia or renal cell carcinoma. Many solid tumours exhibiting low immune activity, i.e., immunologically ‘cold’, such as highly aggressive pancreatic cancers, have correspondingly become regarded as inappropriate for prospective immunotherapeutic modulation. Standard approach in these tumours therefore relies upon early-stage identification and curative surgical resection, an identifiably imperfect option in both progression temporality and deterrence of metastatic disease. Fundamentally predicated upon the therapeutic activation of existing systemic immune resources, selectively towards malignant transformed cellular subpopulations, current cancer immunotherapy heavily utilises monoclonal antibody checkpoint inhibitors (i.e., PD-1, PDL-L1, CTLA-4) influencing resultant upregulation of physiologic immune activation pathways. These correspondingly enhance immunologic function and interfere with carcinogenesis. With ongoing development in the scientific understanding of complex tumour microenvironment interactions and subclonal heterogeneity, increasingly promising investigations have developed. These include the effective management of low immune activity cold solid tumours with original immunogenic cofactor therapies as well as immune modulation in conjunction with co-operative chemotherapeutic, radiological, or surgical intervention. Advancements in novel combination immunotherapies as well as innovative downstream management courses offer great optimism for the applicability of emerging cancer immunotherapy to prospective treatment of cold tumours. This review comprehensively analyses and discusses notable current research directions in the field and underscores future directions for continued scientific progress alongside relevant clinical applications.