Cancer immunotherapy represents an invasive therapeutic approach that orchestrates the body's immune system to combat malignancies [1]. In contrast, the immunotherapeutic modality may impede tumor-associated antigens, thereby antagonizing cellular metastasis. The intricate nature, response dynamics, and mechanisms governing the immune system's functionality concerning cancer cells have been postulated by numerous researchers. Immunotherapy can be broadly categorized into innate and adaptive immunotherapy [2]. The innate immune system primarily executes the phagocytosis of antigen-presenting tumor cells, affecting the direct engulfment of aberrant cells or cellular debris [3]. These abnormal cells comprise proteins associated with antigen-presenting cells, known as major histocompatibility, complex I (MHC I), MHC class I molecules, found on the surface of all nucleated cells, normally display peptides from the cell's own proteins. However, during viral infection, peptides from viral proteins can also be presented [4]. Noteworthy phagocytic cell types include natural killer cells, CD8+ cells, macrophages, dendritic cells, monocytes, eosinophils, basophils, and neutrophils [5].

Conversely, adaptive immunotherapy effectively engages B and T lymphocytes in tumorigenesis. These lymphocytes function as antibodies, inhibiting tumorigenesis by indirectly targeting tumor-associated antigens (TAAs) of tumor cells [6]. Lymphocytes activate their response upon encountering TAAs on the tumor cell surface, enhancing immune responses, inducing apoptosis, and ultimately eliminating these cells [7]. TAAs also facilitate the differentiation between cancerous and normal cells. Innate and adaptive immunotherapies constitute a frontline treatment that commences at the skin and mucous cells or tissues and culminate with B and T lymphocytes [8]. However, these approaches are not comprehensive in detecting, diagnosing, and prognosing cancer.

Novel cancer therapies, such as immunogenic and tolerogenic cell death, have recently emerged to prevent oncogenesis [9]. Immunogenic cell death (ICD) recognizes damage-associated molecular patterns (DAMPs) in cancer cells, eliciting immune responses that lead to cell death [10]. Key components of ICD include calreticulin (CRT) and heat-shock proteins (e.g., HSP90). CRT is externalized on the surface of cancer cells, while HSP90 binds with LRP1, suppressing tumor progression [11]. Tolerogenic cell death, on the other hand, indirectly induces cell death by activating specific cytotoxic B and T lymphocytes and programmed cell death (PD-1) [12]. The resulting apoptotic cells release TGF-β, inhibiting immune responses and promoting self-death, thereby contributing to the prevention of tumorigenesis [13].

A recent study highlights a new era of immunotherapy focused on tumor-targeting immune responses, categorizing immunotherapies into active and passive forms [14]. Active immunotherapy targets cancer cells without mediated receptors, encompassing dendritic cell vaccines, cytokines, checkpoint inhibitors, and adaptive cell therapy [15]. Passive immunotherapy targets anti-tumor immune responses against cancer antigens with in vitro mediated immune responses, providing discrimination between self and non-self immunomodulators. Immune checkpoint inhibitors (ICIs), including CTLA-4, specified chimeric antigen receptors (CAR) T cells, and PD-1, play a pivotal role in active immunotherapy [16]. ICIs exert a significant influence, targeting specific inhibitory receptors on T cells through monoclonal antibodies (mAbs). These receptors, known as immune checkpoint molecules, function as negative regulators, impeding further T cell activation and playing a crucial role in self-tolerance maintenance [17,18]. Dysregulation of these checkpoints by tumor cells often facilitates immune evasion. ICIs, as immunomodulators, bolster antitumor immune responses and have shown remarkable efficacy across various tumor types. Whether administered alone or in conjunction with conventional therapies, ICIs have yielded notable outcomes. They find utility in the treatment of both advanced and metastatic cancer, serving as adjuvant or neoadjuvant therapy even in early-stage cancer management. ICIs stand as a revolutionary breakthrough in cancer treatment [19,20]. ICIs activate the immune response against TAAs by binding with cancer antigen molecules, exemplified by the PD-1 immune checkpoint inhibitors binding to PD-L1 on T cells, blocking the PD-1/PD-L1 pathways, inducing apoptosis, and ultimately leading to cell death. ICIs contribute significantly to the detection, diagnosis, and prognosis of specific cancers such as non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, urothelial, and gastric cancer [21]. Adoptive cell immunotherapy, particularly CAR T cells, with the ability to bind to two different receptors independently of the MHC, adds another dimension to the therapeutic landscape [22].

In the realm of cancer treatment, chemotherapy, an aggressive intervention employing drugs to inhibit cancer progression, can be synergistically combined with immunotherapy for enhanced efficacy [23]. This combination, termed chemoimmunotherapy, presents challenges in delivering drugs to target cells [24]. Innovative drug delivery platforms, including nanoparticles, hydrogels, scaffolds, and vaccines, offer a promising avenue for optimizing cancer treatment. These platforms facilitate drug delivery and enhance drug solubility, stability, efficacy, pharmacokinetics, and pharmacodynamics while minimizing toxicity [25]. Nanoparticles, characterized by ultrafine structures with a 1–100 nm diameter range, represent a notable example. Injectable hydrogels and scaffolds, as crosslinked polymers, contribute to delivering drugs within the body of cancer patients [26]. Combinations of chemotherapeutic drugs with immune checkpoints and targeted antibodies show promise in treating various cancers, including NSCL, bladder, cervical, breast, gastric, pancreatic, and ovarian cancer [27].

Despite the paradigm shift brought about by traditional cancer immunotherapy, challenges persist, with limited response and survival rates due to sensitivity, toxicity, and other factors [28]. Consequently, there is a pressing need for the identification of predictive biomarkers to refine cancer therapy. Predictive biomarkers are invaluable in determining diverse cancer patients' responsiveness and survival rates [29]. Exploring immune biomarkers elucidating the complex interaction between cancer and the immune system holds promise for refining cancer immunotherapeutics [30].

This comprehensive review provides an overview of cancer immunotherapeutic agents, their advanced technologies, and their integration with chemotherapy as a drug-delivery platform. Additionally, it sheds light on prospects related to immune biomarkers, emerging cancer immunotherapies, and novel target delivery platforms for cancer treatment.