Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules

Abstract

Objectives

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

Materials and methods

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry.

Results

All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients.

Conclusions

This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.

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Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules

Abstract

Objectives

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

Materials and methods

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry.

Results

All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients.

Conclusions

This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.

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Huge right ventricular mass lesion associated with genital malignant tumor: a case report

Primary heart tumors are rare, whereas metastatic heart tumors occur more frequently.

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Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules

Abstract

Objectives

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

Materials and methods

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry.

Results

All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients.

Conclusions

This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.

from Cancer via ola Kala on Inoreader http://ift.tt/2kj7j9s
via IFTTT

Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules

Abstract

Objectives

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

Materials and methods

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry.

Results

All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients.

Conclusions

This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.

from Cancer via ola Kala on Inoreader http://ift.tt/2kj7j9s
via IFTTT

Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules

Abstract

Objectives

To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

Materials and methods

We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry.

Results

All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients.

Conclusions

This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.

http://ift.tt/2kj7j9s

Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial

Abstract

Background

Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone.

Methods

Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml⁻¹ remifentanil with 0.05 μg kg⁻¹ h⁻¹ naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml⁻¹ remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery.

Results

The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22–3.84) vs 3.84 (3.76–4.00) vs 3.80 (3.69–4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups.

Conclusions

The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain.

Clinical trial registration

NCT02856087.

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