Handbook of Targeted Cancer Therapy and Immunotherapy

116 knowledge would allow for more precise discrimination of immune targets tailored to tumors with defined molecular or histologic features. Mirroring the experience with mi crosatellite unstable tumors and efficacy of PD-1/PD-L1 blockade antibodies in colorec tal or other tumors, refining personalized approaches can impact care of patients (67). From a methodologic standpoint, more sophisticated spatially oriented and single-cell analyses are also undergoing continued refinement (68). Furthermore, continued deep sequencing approaches will enable better insight into the molecular features of tumors themselves (69). These tools will be powerful and enable rapid scientific advances. Likewise, it will be imperative to continue efforts in developing better animal models, organoid technologies, and ensuring accessibility to human tissues in which to validate hypotheses in the clinical setting (70). Perhaps more consistent efforts at implementing clinical trials to test immuno therapy approaches in the neoadjuvant setting also hold value. Theoretically, this approach would ensure tissue access and direct investigation of therapeutic effects in the human setting. Further, it would enable intervention with immunotherapy approaches earlier during the course of disease and prior to multiple systemic exposures to chemotherapy. Another key limitation in the field is that much of our understanding into immune composition of GI tumors has been established from re section specimens, which capture carcinogenesis at an early to moderate stage. In contrast, across many tumor types, far less is known about the immune composition in the setting of metastasis. This may be particularly true for GI tumors that ultimately present with diffuse liver metastasis such as pancreatic cancer, whereby resection is not warranted and tissues for research and immunologic characterization are more limited. Finally, it is worth noting that great advances may arise from effective cross-disciplinary communication between scientists with diverse research interests and clinical investigators. The close links between cancer immunity with diet, obesity, the microbiome, and other emerging physiologic features are certainly worthy of deeper investigation. Unraveling these relationships in a mechanistic manner may hold important insight related to etiology, preven tion, and therapy of GI cancer (71–73).

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