Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Koh, Jaemoon; Kim, Sehui; Kim, Moon Young; Go, Heounjeong; Jeon, Yoon Kyung; Chung, Doo Hyun

doi:10.18632/oncotarget.14632

Cited by 71 publications

(62 citation statements)

References 33 publications

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“…Ultimately, they found that patients with tumors containing a high density of CD103+ CD8+ T RM cells had significantly better survival than those with tumors containing a low density of CD103+ CD8+ T RM cells. Likewise, two other recent studies have demonstrated a similar link between CD103+ CD8+ T RM cells and patient prognosis in lung cancer (8,9). These survival findings further implicate tumor-infiltrating T cell responses as a crucial component of the tumor-immune microenvironment and identify a unique subset of T cells, CD103+ CD8+ T RM cells, which are likely responsible for the previously reported survival outcomes linked to tumor-infiltrating T cell densities.…”

supporting

confidence: 73%

Transcriptional programs of tumor infiltrating T-cells provide insight into mechanisms of immune response and new targets for immunotherapy

et al. 2017

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Early 2015 marked the first major clinical success of immunotherapy in lung cancer, resulting in the FDA approval of nivolumab (an anti-PD-1 antibody) for metastatic squamous non-small cell lung cancer (NSCLC). A little over a year later, two additional PD-1 blocking agents were approved, atezolizumab and pembrolizumab, f o r u s e i n t h e t r e a t m e n t o f m e t a s t a t i c N S C L C . Pembrolizumab was approved as a first line therapeutic option if a patient's tumor was found to contain at least 50% of tumor cells expressing PD-L1. While immunotherapeutic advancements in lung cancer are promising, response rates to anti-PD-1 therapy in NSCLC have been poor, ranging from 15-50% (1-3), even when prospectively screening tumors for PD-L1 expression before therapeutic intervention. Likewise, clinical response has been observed for anti-PD-1 agents independent of a tumor's baseline PD-L1 status (4-6), which further complicates clinical decision making in the assessment of optimal therapy for NSCLC. A great deal of additional research is necessary to determine the best use of checkpoint inhibitors in lung cancer and the best set of tumor-immune features for determining durable clinical response.The recent publication by Ganesan et al. in Nature Immunology (7) highlights the need for a deeper understanding of the immunological state of lung tumors to determine how the immune landscape of lung tumors may predispose patients for better or worse outcomes. The authors investigated the molecular features associated with robust anti-tumor immune responses by extracting tumorinfiltrating and adjacent-normal T cells from surgically resected NSCLC specimens and utilizing RNA-seq to analyze the transcriptional programs of these immune cells. Marked differences in the transcriptional landscape were found in tumor infiltrating T cells when compared to their adjacent-normal T cell counterparts. Likewise, they characterized similar transcriptional program profiles in tumor-infiltrating T cells derived from head and neck squamous cell carcinoma (HNSCC), ultimately validating their T cell findings and further suggesting that a core set of regulatory programs may define tumor-infiltrating leukocytes across multiple tumor types. Major players in the active transcriptional programing of tumor-infiltrating T cells appeared to be related to T cell exhaustion, cell-cycle regulation, and T cell receptor activation. Most significantly, exhaustion signatures were found to be upregulated in the tumor-infiltrating T cells, a gene set containing the clinically relevant immunotherapeutic targets such as PD-1, CTLA-4, and TIM-3.The authors also noted significant heterogeneity in the expression of these clinically relevant T cell exhaustion targets among the tumor-infiltrating T cells, which they highlighted may account for the person-to-person variability

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confidence: 73%

Transcriptional programs of tumor infiltrating T-cells provide insight into mechanisms of immune response and new targets for immunotherapy

et al. 2017

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“…Studies analyzing the infiltration of T RM cells in human tumors have shed some light on their relevance in anti‐tumor immunity. Tumor infiltration of CD8 + T cells exhibiting a resident phenotype (CD69 + CD103 + and/or CD103 + ) correlates with a more favorable prognosis for various human cancers (Djenidi et al, ; Koh et al, ; Wang et al, ; Webb, Milne, Watson, Deleeuw, & Nelson, ). Similar correlations were shown for human melanoma (Edwards et al, ; Murray et al, ) (Figure ).…”

Section: Skin‐resident T‐cell Responses In Melanomamentioning

confidence: 99%

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Willemsen

Linkutė

Luiten

et al. 2019

Pigment Cell Melanoma Res

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Tissue‐resident memory T (TRM) cells are abundant in the memory T cell pool and remain resident in peripheral tissues, such as the skin, where they act as alarm sensors or cytotoxic killers. TRM cells persist long after the pathogen is eliminated and can respond rapidly upon reinfection with the same antigen. When aberrantly activated, skin‐located TRM cells have a profound role in various skin disorders, including vitiligo and melanoma. Autoreactive TRM cells are present in human lesional vitiligo skin and mouse models of vitiligo, which suggests that targeting these cells could be effective as a durable treatment strategy for vitiligo. Furthermore, emerging evidence indicates that induction of melanoma‐reactive TRM cells is needed to achieve effective protection against tumor growth. This review highlights seminal reports about skin‐resident T cells, focusing mainly on their role in the context of vitiligo and melanoma, as well as their potential as therapeutic targets in both diseases.

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“…PD-1 expression in lymphocytes was evaluated intratumourally, based on the number of positive TILs counted in three high-power fields (HPF) (400-fold magnification) of highest density. Stratification was made for negative expression (0-5), weak (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), moderate (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) or strong (>30) infiltration patterns.…”

Section: E V a L U A T I O N O F I M M U N O H I S T O C H E M I C A mentioning

confidence: 99%

“…The prognostic significance of TILs has been evaluated in several malignancies, including breast cancer, non-small-cell lung cancer and oesophageal squamous cell carcinoma, revealing better clinical outcome when high levels of TILs are present. [6][7][8] In HNSCC, high levels of TILs are associated with favourable patient survival. [9][10][11][12] However, studies focusing on the prognostic relevance of PD-1-expressing TILs in HNSCC are sparse.…”

Section: Introductionmentioning

confidence: 99%

PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome

Schneider¹,

Kadletz²,

Wiebringhaus

et al. 2018

Histopathology

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Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Cited by 71 publications

References 33 publications

Transcriptional programs of tumor infiltrating T-cells provide insight into mechanisms of immune response and new targets for immunotherapy

Transcriptional programs of tumor infiltrating T-cells provide insight into mechanisms of immune response and new targets for immunotherapy

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

PD‐1 and PD‐L1 expression in HNSCC primary cancer and related lymph node metastasis – impact on clinical outcome

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