Abstract
Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as chemotherapy, radiation, or vaccines, which can stimulate the immune system and recruit antitumor T cells into the tumor bed, may be a relevant strategy to increase the proportion of responding patients. Such an approach still raises the following questions: What are the immunological features modulated by immunogenic therapies that can be critical to ensure not only immediate but also long-lasting tumor protection? How must the combined treatments be administered to the patients to harness their full potential while limiting adverse immunological events? Here, we address these points by reviewing how immunogenic anticancer therapies can provide novel therapeutic opportunities upon combination with ICPi. We discuss their ability to create a permissive tumor microenvironment through the generation of inflamed tumors and stimulation of memory T cells such as resident (TRM) and stem-cell like (TSCM) cells. We eventually underscore the importance of sequence, dose, and duration of the combined anticancer therapies to design optimal and successful cancer immunotherapy strategies.
Highlights
It is well-established that the emergence and propagation of tumor cells are initially controlled by the immune system of the host [1]
This is underscored by observations that in lung cancer patients treated by platinum-based chemotherapy, the benefit of having a pre-existing antitumor T cell immunity before treatment was only notable in patients with a controlled tumor burden
The use of immunogenic therapies to overcome resistance to immune checkpoint inhibitors (ICPi) is based on evidence that the accumulation of ICP+ T cells with effector functions within the tumor before ICPi therapy is associated with a good prognosis
Summary
It is well-established that the emergence and propagation of tumor cells are initially controlled by the immune system of the host [1]. In clinical settings, mono- or poly-conventional therapies often fail to achieve complete cancer cure and long-term survival Vaccines are another type of immunogenic anticancer therapy, which relies on immunizing patients against tumor antigens and induces a specific effector and memory T cell immunity against tumor cells. Tcell reactivation or prevent their dysfunction by the use of blocking monoclonal antibodies targeting immunosuppressive molecules such as CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), PD-1 (Programmed cell death 1), and TIM-3 (T-cell immunoglobulin mucin-3), which are called immune checkpoints Despite this significant progress, a substantial number of patients are unresponsive to ICPi therapy from the very start [23], while others progressively develop a resistance to treatment [24].
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