Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination With Immunotherapy

Abstract

There have been significant advances in cancer treatment over the past several years through the use of chemotherapy, radiation therapy, molecularly targeted therapy, and immunotherapy. Despite these advances, treatments such as monotherapy or monomodality have significant limitations. There is increasing interest in using these strategies in combination; however, it is not completely clear how best to incorporate molecularly targeted and immune-targeted therapies into combination regimens. This is particularly pertinent when considering combinations with immunotherapy, as other types of therapy may have significant impact on host immunity, the tumor microenvironment, or both. Thus, the influence of chemotherapy, radiation therapy, and molecularly targeted therapy on the host anti-tumor immune response and the host anti-host response (ie, autoimmune toxicity) must be taken into consideration when designing immunotherapy-based combination regimens. We present data related to many of these combination approaches in the context of investigations in patients with melanoma and discuss their potential relationship to management of patients with other tumor types. Importantly, we also highlight challenges of these approaches and emphasize the need for continued translational research.

Neogenin, Defined as a GD3-associated Molecule by Enzyme-mediated Activation of Radical Sources, Confers Malignant Properties via Intracytoplasmic Domain in Melanoma Cells

“…Malignant melanomas have been one of the most refractory diseases despite of a number of clinical trials toward complete cure (52,53). mAbs reactive with GD3 has been expected to open a new dimension in the melanoma therapy (54) and showed some promising results (16,55) by modulating the molecular forms (56 -58).…”

Nanomedicine of synergistic drug combinations for cancer therapy – Strategies and perspectives

“…These new combination therapies include chemotherapy with immunotherapy, chemotherapy with targeted therapy, chemotherapy with gene ( i.e. DNA- and RNA-based) therapy or epigenetic therapy, and immunotherapy with targeted therapy [12-20]. …”

Cause‐specific mortality after diagnosis of cancer among HIV‐positive patients: A collaborative analysis of cohort studies

“…Mortality rates after diagnosis of cancer were lower during 2006–2015 than 1996–2005: these declines were not explained by changes in CD4 count and viral load at cancer diagnosis. Possible explanations are earlier cancer stage at diagnosis due to improvements in screening, improvements in care among PLHIV, greater awareness of drug–drug interactions, availability of more effective treatment for cancer or patients with higher CD4 counts being able to withstand more doses of chemotherapy …”

“…The improvement in survival of PLHIV diagnosed with cancer in 2006–2015 compared to 1996–2005 may reflect improvements in care among PLHIV, such as increased cancer screening resulting in earlier detection of cancers, which are easier to treat, or more effective cancer treatment . Another explanation could be improvements in ART resulting in better immunological status at cancer diagnosis, leading to more patients being able to tolerate chemotherapy …”