Tumor-Infiltrating Lymphocytes in the Checkpoint Inhibitor Era

Linette, Gerald P.; Carreño, Beatriz M.

doi:10.1007/s11899-019-00523-x

Cited by 67 publications

(46 citation statements)

References 52 publications

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“…Increased levels of TILs correlate with a favorable microenvironment and improved prognosis in several studies across multiple tumor types. 98 This approach consists of harvesting and culturing lymphocytes from excised tumor tissue, followed by testing for responsiveness to specific neoepitopes. Lymphocytes predicted to recognize tumor antigens with high affinity are expanded ex vivo and reinfused into the patient.…”

Section: Indirect Modulation Of Tumor Immunogenicity Markers Of An Immentioning

confidence: 99%

The future of cancer immunotherapy: microenvironment-targeting combinations

2020

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Immunotherapy holds the potential to induce durable responses, but only a minority of patients currently respond. The etiologies of primary and secondary resistance to immunotherapy are multifaceted, deriving not only from tumor intrinsic factors, but also from the complex interplay between cancer and its microenvironment. In addressing frontiers in clinical immunotherapy, we describe two categories of approaches to the design of novel drugs and combination therapies: the first involves direct modification of the tumor, while the second indirectly enhances immunogenicity through alteration of the microenvironment. By systematically addressing the factors that mediate resistance, we are able to identify mechanistically-driven novel approaches to improve immunotherapy outcomes.

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Section: Indirect Modulation Of Tumor Immunogenicity Markers Of An Immentioning

confidence: 99%

The future of cancer immunotherapy: microenvironment-targeting combinations

2020

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“…A positive association exists between the accumulation of tumor‐infiltrating CD8 T cells in the treatment‐naive setting and favorable clinical outcomes in patients with most types of solid tumors, RCC being a notable exception . However, it is widely recognized that the tumor microenvironment suppresses CD8 T cell effector function through a variety of mechanisms that have been thoroughly reviewed by others .…”

Section: Tumor Cell Metabolism As a Driver Of Tumor‐infiltrating Lympmentioning

confidence: 99%

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

Turbitt

Rosean

Weber

et al. 2020

Immunological Reviews

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Obesity is an established risk factor for many cancers and has recently been found to alter the efficacy of T cell–based immunotherapies. Currently, however, the effects of obesity on immunometabolism remain unclear. Understanding these associations is critical, given the fact that T cell metabolism is tightly linked to effector function. Thus, any obesity‐associated changes in T cell bioenergetics are likely to drive functional changes at the cellular level, alter the metabolome and cytokine/chemokine milieu, and impact cancer immunotherapy outcomes. Here, we provide a brief overview of T cell metabolism in the presence and absence of solid tumor growth and summarize current literature regarding obesity‐associated changes in T cell function and bioenergetics. We also discuss recent findings related to the impact of host obesity on cancer immunotherapy outcomes and present potential mechanisms by which T cell metabolism may influence therapeutic efficacy. Finally, we describe promising pharmaceutical therapies that are being investigated for their ability to improve CD8 T cell metabolism and enhance cancer immunotherapy outcomes in patients, regardless of their obesity status.

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“…Moreover, the application of Immunoscore to HNSCC showed a prognostic advantage for T cell rich tumors [ 49 , 50 ]. Similarly, tumors, including HNSCC, highly infiltrated by CD8+ T cells have a better outcome after immunotherapy than poorly infiltrated ones [ 51 , 52 ]. Overall, these findings suggest that CD8+ T cells play a role in the control of HNSCC growth, a role that is likely hampered by their progressive alteration, leading to tumor escape and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer

Fenoglio

Belgioia

Parodi

et al. 2021

Cancers

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Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28- T cells, and CD8+CD28-CD127-CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28- T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28-CD127-CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition.

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Tumor-Infiltrating Lymphocytes in the Checkpoint Inhibitor Era

Cited by 67 publications

References 52 publications

The future of cancer immunotherapy: microenvironment-targeting combinations

The future of cancer immunotherapy: microenvironment-targeting combinations

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer

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